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Carter P. Bispecific human IgG by design. J Immunol Methods. 248:2001;7-15.
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Anti-CD16/CD30 bispecific antibody treatment for Hodgkin's disease: Role of infusion schedule and costimulation with cytokines
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Hartmann F., Renner C., Jung W., da Costa L., Tembrink S., Held G., Sek A., König J., Bauer S., Kloft M., Pfreundschuh M. Anti-CD16/CD30 bispecific antibody treatment for Hodgkin's disease: role of infusion schedule and costimulation with cytokines. Clin Cancer Res. 7:2001;1873-1881.
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Phase I trial of the novel bispecific molecule H22xKi-4 in patients with refractory Hodgkin lymphoma
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Borchmann P., Schnell R., Fuss I., Manzke O., Davis T., Lewis L.D., Behnke D., Wickenhauser C., Schiller P., Diehl V., Engert A. Phase I trial of the novel bispecific molecule H22xKi-4 in patients with refractory Hodgkin lymphoma. Blood. 100:2002;3101-3107.
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Pharmacokinetic-pharmacodynamic relationships of the bispecific antibody MDX-H210 when administered in combination with interferon gamma: A multiple-dose phase-I study in patients with advanced cancer which overexpresses HER-2/neu
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Lewis L.D., Cole B.F., Wallace P.K., Fisher J.L., Waugh M., Guyre P.M., Fanger M.W., Curnow R.T., Kaufman P.A., Ernstoff M.S. Pharmacokinetic-pharmacodynamic relationships of the bispecific antibody MDX-H210 when administered in combination with interferon gamma: a multiple-dose phase-I study in patients with advanced cancer which overexpresses HER-2/neu. J Immunol Methods. 248:2001;149-165.
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Lewis, L.D.1
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A phase II study of the bispecific antibody MDX-H210 (anti-HER2 x CD64) with GM-CSF in HER2+ advanced prostate cancer
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James N.D., Atherton P.J., Jones J., Howie A.J., Tchekmedyian S., Curnow R.T. A phase II study of the bispecific antibody MDX-H210 (anti-HER2 x CD64) with GM-CSF in HER2+ advanced prostate cancer. Br J Cancer. 85:2001;152-156.
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10
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Bispecific antibody-targeted phagocytosis of HER-2/neu expressing tumor cells by myeloid cells activated in vivo
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Wallace P.K., Kaufman P.A., Lewis L.D., Keler T., Givan A.L., Fisher J.L., Waugh M.G., Wahner A.E., Guyre P.M., Fanger M.W., Ernstoff M.S. Bispecific antibody-targeted phagocytosis of HER-2/neu expressing tumor cells by myeloid cells activated in vivo. J Immunol Methods. 248:2001;167-182.
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Schweizer C., Strauss G., Lindner M., Marme A., Deo Y.M., Moldenhauer G. Efficient carcinoma cell killing by activated polymorphonuclear neutrophils targeted with an Ep-CAM X CD64 (HEA125 X 197) bispecific antibody. Cancer Immunol Immunother. 51:2002;621-629.
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Synergistic antitumor effect of bispecific CD19 X CD3 and CD19 X CD16 diabodies in a preclinical model of non-Hodgkin's lymphoma
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Kipriyanov S.M., Cochlovius B., Schäfer H.J., Moldenhauer G., Bähre A., Le Gall F., Knackmass S., Little M. Synergistic antitumor effect of bispecific CD19 X CD3 and CD19 X CD16 diabodies in a preclinical model of non-Hodgkin's lymphoma. J Immunol. 169:2002;137-144.
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13
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Sundarapandiyan K., Keler T., Behnke D., Engert A., Barth S., Matthey B., Deo Y.M., Graziano R.F. Bispecific antibody-mediated destruction of Hodgkin's lymphoma cells. J Immunol Methods. 248:2001;113-123.
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Sundarapandiyan, K.1
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Graziano, R.F.8
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14
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0035251734
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Mechanisms of G-CSF- or GM-CSF-stimulated tumor cell killing by Fc receptor-directed bispecific antibodies
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The authors present a comparison of bispecific antibodies in which one specificity was anti-CD20 or anti-HER2, and the other was anti-FcγRI, anti-FcγRIII or anti-FcαRI. Whereas the anti-FcγR were more effective in recruiting mononuclear cells, the anti-FcαRI were better with polymorphonuclear cells.
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Stockmeyer B., Elsasser D., Dechant M., Repp R., Gramatzki M., Glennie M.J., van de Winkel J.G.J., Valerius T. Mechanisms of G-CSF- or GM-CSF-stimulated tumor cell killing by Fc receptor-directed bispecific antibodies. J Immunol Methods. 248:2001;103-111 The authors present a comparison of bispecific antibodies in which one specificity was anti-CD20 or anti-HER2, and the other was anti-FcγRI, anti-FcγRIII or anti-FcαRI. Whereas the anti-FcγR were more effective in recruiting mononuclear cells, the anti-FcαRI were better with polymorphonuclear cells.
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J Immunol Methods
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Stockmeyer, B.1
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Van de Winkel, J.G.J.7
Valerius, T.8
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15
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0037114641
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Chimeric IgA antibodies against HLA class II effectively trigger lymphoma cell killing
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A comparison of the antitumor efficacy of anti-HLA class II chimeric antibodies (i.e. with the same variable domains and different human IgG and IgA constant domains). Of note is that IgG and IgA utilized different cell types to effect tumor cell killing.
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Dechant M., Vidarsson G., Stockmeyer B., Repp R., Glennie M.J., Gramatzki M., van de Winkel J.G.J., Valerius T. Chimeric IgA antibodies against HLA class II effectively trigger lymphoma cell killing. Blood. 100:2002;4574-4580 A comparison of the antitumor efficacy of anti-HLA class II chimeric antibodies (i.e. with the same variable domains and different human IgG and IgA constant domains). Of note is that IgG and IgA utilized different cell types to effect tumor cell killing.
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Blood
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Dechant, M.1
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Van de Winkel, J.G.J.7
Valerius, T.8
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16
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0035872491
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Enhancement of polymorphonuclear cell-mediated tumor cell killing on simultaneous engagement of FcγRI (CD64) and FcαRI (CD89)
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This study shows that FcγRI and FcαRI not only function independently in tumor cell lysis but also augment one another. This underscores the potential use of single engineered antibodies that could activate both or a combination of two antibodies, one that engaged FcγRI and another that engaged FcαRI.
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van Egmond M., van Spriel A.B., Vermeulen H., Huls G., van Garderen E., van de Winkel J.G.J. Enhancement of polymorphonuclear cell-mediated tumor cell killing on simultaneous engagement of FcγRI (CD64) and FcαRI (CD89). Cancer Res. 61:2001;4055-4060 This study shows that FcγRI and FcαRI not only function independently in tumor cell lysis but also augment one another. This underscores the potential use of single engineered antibodies that could activate both or a combination of two antibodies, one that engaged FcγRI and another that engaged FcαRI.
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Cancer Res
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Van Egmond, M.1
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Van de Winkel, J.G.J.6
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17
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0036918104
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Antibody-cytokine fusion proteins: Harnessing the combined power of cytokines and antibodies for cancer therapy
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A concise review of, and good introduction to, antibody-cytokine fusion proteins.
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Helguera G., Morrison S.L., Penichet M.L. Antibody-cytokine fusion proteins: harnessing the combined power of cytokines and antibodies for cancer therapy. Clin Immunol. 103:2002;233-246 A concise review of, and good introduction to, antibody-cytokine fusion proteins.
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Clin Immunol
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Helguera, G.1
Morrison, S.L.2
Penichet, M.L.3
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18
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0036493867
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Enhancement of the antitumor properties of interleukin-2 by its targeted delivery to the tumor blood vessel extracellular matrix
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Carnemolla B., Borsi L., Balza E., Castellani P., Meazza R., Berndt A., Ferrini S., Kosmehl H., Neri D., Zardi L. Enhancement of the antitumor properties of interleukin-2 by its targeted delivery to the tumor blood vessel extracellular matrix. Blood. 99:2002;1659-1665.
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Blood
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Carnemolla, B.1
Borsi, L.2
Balza, E.3
Castellani, P.4
Meazza, R.5
Berndt, A.6
Ferrini, S.7
Kosmehl, H.8
Neri, D.9
Zardi, L.10
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19
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0035866345
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The level of MHC class I expression on murine adenocarcinoma can change the antitumor effector mechanism of immunocytokine therapy
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Using an anti-EpCAM-IL-2 fusion in vitro and in vivo, the authors showed that low levels of MHC class I on tumor cells favor killing via natural killer cells. In conjunction with earlier studies showing that high MHC class I elicits a T-cell response, both mechanisms may play a role in patients' response dependent on the MHC class I level on their tumor.
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Imboden M., Murphy K.R., Rakhmilevich A.L., Neal Z.C., Xiang R., Reisfeld R.A., Gillies S.D., Sondel P.M. The level of MHC class I expression on murine adenocarcinoma can change the antitumor effector mechanism of immunocytokine therapy. Cancer Res. 61:2001;1500-1507 Using an anti-EpCAM-IL-2 fusion in vitro and in vivo, the authors showed that low levels of MHC class I on tumor cells favor killing via natural killer cells. In conjunction with earlier studies showing that high MHC class I elicits a T-cell response, both mechanisms may play a role in patients' response dependent on the MHC class I level on their tumor.
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(2001)
Cancer Res
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Imboden, M.1
Murphy, K.R.2
Rakhmilevich, A.L.3
Neal, Z.C.4
Xiang, R.5
Reisfeld, R.A.6
Gillies, S.D.7
Sondel, P.M.8
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20
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0035059013
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A recombinant IgG3-(IL-2) fusion protein for the treatment of human HER2/neu expressing tumors
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Penichet M.L., Dela Cruz J.S., Shin S.-U., Morrison S.L. A recombinant IgG3-(IL-2) fusion protein for the treatment of human HER2/neu expressing tumors. Hum Antibodies. 10:2001;43-49.
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Hum Antibodies
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Penichet, M.L.1
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Morrison, S.L.4
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21
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0036254260
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Enhanced inhibition of tumor growth and metastasis, and induction of antitumor immunity by IL-2-IgG2b fusion protein
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Budagian V., Nanni P., Lollini P.L., Musiani P., Di Carlo E., Bulanova E., Paus R., Bulfone-Paus S. Enhanced inhibition of tumor growth and metastasis, and induction of antitumor immunity by IL-2-IgG2b fusion protein. Scand J Immunol. 55:2002;484-492.
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Scand J Immunol
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Budagian, V.1
Nanni, P.2
Lollini, P.L.3
Musiani, P.4
Di Carlo, E.5
Bulanova, E.6
Paus, R.7
Bulfone-Paus, S.8
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22
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0036042603
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Bi-functional cytokine fusion proteins for gene therapy and antibody-targeted treatment of cancer
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The design of fusion proteins with two different cytokines fused in multiple modes to both scFv and IgG. These creative constructs provide both localization and resultant synergy for the cytokines in antitumor applications.
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Gillies S.D., Lan Y., Brunkhorst B., Wong W.K., Li Y., Lo K.M. Bi-functional cytokine fusion proteins for gene therapy and antibody-targeted treatment of cancer. Cancer Immunol Immunother. 51:2002;449-460 The design of fusion proteins with two different cytokines fused in multiple modes to both scFv and IgG. These creative constructs provide both localization and resultant synergy for the cytokines in antitumor applications.
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Cancer Immunol Immunother
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Gillies, S.D.1
Lan, Y.2
Brunkhorst, B.3
Wong, W.K.4
Li, Y.5
Lo, K.M.6
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23
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0036194917
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Enhancement of the antitumor activity of interleukin-12 by targeted delivery to neovasculature
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Halin C., Rondini S., Nilsson F., Berndt A., Kosmehl H., Zardi L., Neri D. Enhancement of the antitumor activity of interleukin-12 by targeted delivery to neovasculature. Nat Biotechnol. 20:2002;264-269.
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Nat Biotechnol
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Halin, C.1
Rondini, S.2
Nilsson, F.3
Berndt, A.4
Kosmehl, H.5
Zardi, L.6
Neri, D.7
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24
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0034787465
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Mechanism of antitumor activity of a single-chain interleukin-12 IgG3 antibody fusion protein (mscIL-12.her2.IgG3)
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The first study comparing IL-12 versus antibody-IL-12 fusion in vivo underscores that therapeutics may have complex, multiple modes of action.
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Peng L.S., Penichet M.L., Dela Cruz J.S., Sampogna S.L., Morrison S.L. Mechanism of antitumor activity of a single-chain interleukin-12 IgG3 antibody fusion protein (mscIL-12.her2.IgG3). J Interferon Cytokine Res. 21:2001;709-720 The first study comparing IL-12 versus antibody-IL-12 fusion in vivo underscores that therapeutics may have complex, multiple modes of action.
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J Interferon Cytokine Res
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, pp. 709-720
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Peng, L.S.1
Penichet, M.L.2
Dela Cruz, J.S.3
Sampogna, S.L.4
Morrison, S.L.5
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25
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0037471398
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Protein vaccination with the HER2/neu extracellular domain plus anti-HER2/neu antibody-cytokine fusion proteins induces a protective anti-HER2/neu immune response in mice
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Vaccination of mice with HER2 extracellular domain plus three different immunocytokines (human IgG3 with IL-2, IL-12 or GM-CSF) showed antitumor effect on a syngeneic carcinoma expressing rat HER2 (compared to vaccination with HER2 alone or HER2 plus IgG3). The influence of the murine antibody isotype on the response to the immunocytokines is also discussed.
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Dela Cruz J.S., Lau S.Y., Ramirez E.M., De Giovanni C., Forni G., Morrison S.L., Penichet M.L. Protein vaccination with the HER2/neu extracellular domain plus anti-HER2/neu antibody-cytokine fusion proteins induces a protective anti-HER2/neu immune response in mice. Vaccine. 21:2003;1317-1326 Vaccination of mice with HER2 extracellular domain plus three different immunocytokines (human IgG3 with IL-2, IL-12 or GM-CSF) showed antitumor effect on a syngeneic carcinoma expressing rat HER2 (compared to vaccination with HER2 alone or HER2 plus IgG3). The influence of the murine antibody isotype on the response to the immunocytokines is also discussed.
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Vaccine
, vol.21
, pp. 1317-1326
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Dela Cruz, J.S.1
Lau, S.Y.2
Ramirez, E.M.3
De Giovanni, C.4
Forni, G.5
Morrison, S.L.6
Penichet, M.L.7
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26
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0035030604
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Antibody engineering for targeted therapy of cancer: Recombinant Fv-immunotoxins
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Niv R., Cohen C.J., Denkberg G., Segal D., Reiter Y. Antibody engineering for targeted therapy of cancer: recombinant Fv-immunotoxins. Curr Pharm Biotechnol. 2:2001;19-46.
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Curr Pharm Biotechnol
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Niv, R.1
Cohen, C.J.2
Denkberg, G.3
Segal, D.4
Reiter, Y.5
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27
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0036285666
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A phase I study with an anti-CD30 ricin A-chain immunotoxin (Ki-4.dgA) in patients with refractory CD30+ Hodgkin's and non-Hodgkin's lymphoma
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Schnell R., Staak O., Borchmann P., Schwartz C., Matthey B., Hansen H., Schindler J., Ghetie V., Vitetta E.S., Diehl V., Engert A. A phase I study with an anti-CD30 ricin A-chain immunotoxin (Ki-4.dgA) in patients with refractory CD30+ Hodgkin's and non-Hodgkin's lymphoma. Clin Cancer Res. 8:2002;1779-1786.
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Clin Cancer Res
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Schnell, R.1
Staak, O.2
Borchmann, P.3
Schwartz, C.4
Matthey, B.5
Hansen, H.6
Schindler, J.7
Ghetie, V.8
Vitetta, E.S.9
Diehl, V.10
Engert, A.11
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28
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0036793823
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A phase I trial of the single-chain immunotoxin SGN-10 (BR96 sFv-PE40) in patients with advanced solid tumors
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Posey J.A., Khazaeli M.B., Bookman M.A., Nowrouzi A., Grizzle W.E., Thornton J., Carey D.E., Lorenz J.M., Sing A.P., Siegall C.B.et al. A phase I trial of the single-chain immunotoxin SGN-10 (BR96 sFv-PE40) in patients with advanced solid tumors. Clin Cancer Res. 8:2002;3092-3099.
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Clin Cancer Res
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Posey, J.A.1
Khazaeli, M.B.2
Bookman, M.A.3
Nowrouzi, A.4
Grizzle, W.E.5
Thornton, J.6
Carey, D.E.7
Lorenz, J.M.8
Sing, A.P.9
Siegall, C.B.10
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0030862195
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Vascular leak syndrome: A side effect of immunotherapy
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Baluna R., Vitetta E.S. Vascular leak syndrome: a side effect of immunotherapy. Immunopharmacology. 37:1999;117-132.
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Immunopharmacology
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Baluna, R.1
Vitetta, E.S.2
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30
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0037382907
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Genetic engineering of an immunotoxin to eliminate pulmonary vascular leak in mice
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Following previous identification of a common motif in protein toxins widely used in immunotoxins that effects vascular leak syndrome (a major side effect), this study describes the engineering of a deglycosylated ricin toxin A chain to alter the motif. Interestingly, alterations outside of but near the motif proved better than alterations within the motif.
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Smallshaw J.E., Ghetie V., Rizo J., Fulmer J.R., Trahan L.L., Ghetie M.A., Vitetta E.S. Genetic engineering of an immunotoxin to eliminate pulmonary vascular leak in mice. Nat Biotechnol. 21:2003;387-391 Following previous identification of a common motif in protein toxins widely used in immunotoxins that effects vascular leak syndrome (a major side effect), this study describes the engineering of a deglycosylated ricin toxin A chain to alter the motif. Interestingly, alterations outside of but near the motif proved better than alterations within the motif.
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(2003)
Nat Biotechnol
, vol.21
, pp. 387-391
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Smallshaw, J.E.1
Ghetie, V.2
Rizo, J.3
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Trahan, L.L.5
Ghetie, M.A.6
Vitetta, E.S.7
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31
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0036237495
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Specifically targeting the CD22 receptor of human B cell lymphomas with RNA damaging agents: A new generation of therapeutics
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Hursey M., Newton D.L., Hansen H.J., Ruby D., Goldenberg D.M., Rybak S.M. Specifically targeting the CD22 receptor of human B cell lymphomas with RNA damaging agents: a new generation of therapeutics. Leuk Lymphoma. 43:2002;953-959.
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Hursey, M.1
Newton, D.L.2
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0035980983
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Selective activation of anticancer prodrugs by monoclonal antibody-enzyme conjugates
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Senter P.D., Springer C.J. Selective activation of anticancer prodrugs by monoclonal antibody-enzyme conjugates. Adv Drug Deliv Rev. 53:2001;247-264.
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Adv Drug Deliv Rev
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33
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0034783354
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Influence of relative binding affinity on efficacy in a panel of anti-CD3 scFv immunotoxins
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In addition to correlation between increased affinity/valency and increased efficacy (confounded by differences in epitope between the antibodies), this study underscores the importance of the placement of the toxin relative to the antibody (i.e. at the N or C termini of the antibody) in a panel of immunotoxins.
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Hexham J.M., Dudas D., Hugo R., Thompson J., King V., Dowling C., Neville D.M. Jr., Digan M.E., Lake P. Influence of relative binding affinity on efficacy in a panel of anti-CD3 scFv immunotoxins. Mol Immunol. 38:2001;397-408 In addition to correlation between increased affinity/valency and increased efficacy (confounded by differences in epitope between the antibodies), this study underscores the importance of the placement of the toxin relative to the antibody (i.e. at the N or C termini of the antibody) in a panel of immunotoxins.
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Mol Immunol
, vol.38
, pp. 397-408
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Hexham, J.M.1
Dudas, D.2
Hugo, R.3
Thompson, J.4
King, V.5
Dowling, C.6
Neville D.M., Jr.7
Digan, M.E.8
Lake, P.9
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34
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0035251637
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Selection of cell binding and internalizing epidermal growth factor receptor antibodies from a phage display library
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Representative of a series of papers that describe strategies for the selection from phage libraries of scFv that bind to the target (in this case, epidermal growth factor receptor) and show enhanced internalization. Such antibodies have potential for improving the delivery of conjugated antibodies, such as immunotoxins, and immunoliposomes.
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Heitner T., Moor A., Garrison J.L., Marks C., Hasan T., Marks J.D. Selection of cell binding and internalizing epidermal growth factor receptor antibodies from a phage display library. J Immunol Methods. 248:2001;17-30 Representative of a series of papers that describe strategies for the selection from phage libraries of scFv that bind to the target (in this case, epidermal growth factor receptor) and show enhanced internalization. Such antibodies have potential for improving the delivery of conjugated antibodies, such as immunotoxins, and immunoliposomes.
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(2001)
J Immunol Methods
, vol.248
, pp. 17-30
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Heitner, T.1
Moor, A.2
Garrison, J.L.3
Marks, C.4
Hasan, T.5
Marks, J.D.6
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35
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0037373986
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De novo identification of tumor-specific internalizing human antibody-receptor pairs by phage display methods
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Gao C., Mao S., Ronca F., Zhuang S., Quaranta V., Wirsching P., Janda K.D. De novo identification of tumor-specific internalizing human antibody-receptor pairs by phage display methods. J Immunol Methods. 274:2003;185-197.
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(2003)
J Immunol Methods
, vol.274
, pp. 185-197
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-
Gao, C.1
Mao, S.2
Ronca, F.3
Zhuang, S.4
Quaranta, V.5
Wirsching, P.6
Janda, K.D.7
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36
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0037135703
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Therapeutic efficacy of anti-ErbB2 immunoliposomes targeted by a phage antibody selected for cellular endocytosis
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Nielsen U.B., Kirpotin D.B., Pickering E.M., Hong K., Park J.W., Shalaby M.R., Shao Y., Benz C.C., Marks J.D. Therapeutic efficacy of anti-ErbB2 immunoliposomes targeted by a phage antibody selected for cellular endocytosis. Biochim Biophys Acta. 1591:2002;109-118.
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(2002)
Biochim Biophys Acta
, vol.1591
, pp. 109-118
-
-
Nielsen, U.B.1
Kirpotin, D.B.2
Pickering, E.M.3
Hong, K.4
Park, J.W.5
Shalaby, M.R.6
Shao, Y.7
Benz, C.C.8
Marks, J.D.9
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37
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0037115543
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Internalizing antibodies are necessary for improved therapeutic efficacy of antibody-targeted liposomal drugs
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This comparison of the anti-B cell efficacy of immunoliposomes directed against either a noninternalizing target (CD20) or an internalizing target (CD19) emphasizes that proper target choice can make the difference.
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Sapra P., Allen T.M. Internalizing antibodies are necessary for improved therapeutic efficacy of antibody-targeted liposomal drugs. Cancer Res. 62:2002;7190-7194 This comparison of the anti-B cell efficacy of immunoliposomes directed against either a noninternalizing target (CD20) or an internalizing target (CD19) emphasizes that proper target choice can make the difference.
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(2002)
Cancer Res
, vol.62
, pp. 7190-7194
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Sapra, P.1
Allen, T.M.2
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38
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0036554863
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Anti-HER2 immunoliposomes: Enhanced efficacy attributable to targeted delivery
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A good example of how immunoliposome technology can affect antitumor efficacy while simultaneously reducing the systemic toxicity of a chemotherapeutic.
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Park J.W., Hong K., Kirpotin D.B., Colbern G., Shalaby R., Baselga J., Shan Y., Nielsen U.B., Marks J.D., Moore D.et al. Anti-HER2 immunoliposomes: enhanced efficacy attributable to targeted delivery. Clin Cancer Res. 8:2002;1172-1181 A good example of how immunoliposome technology can affect antitumor efficacy while simultaneously reducing the systemic toxicity of a chemotherapeutic.
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(2002)
Clin Cancer Res
, vol.8
, pp. 1172-1181
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-
Park, J.W.1
Hong, K.2
Kirpotin, D.B.3
Colbern, G.4
Shalaby, R.5
Baselga, J.6
Shan, Y.7
Nielsen, U.B.8
Marks, J.D.9
Moore, D.10
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39
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0036649819
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Cytotoxic targeting of F9 teratocarcinoma tumors with anti-ED-B fibronectin scFv antibody modified liposomes
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Marty C., Odermatt B., Schott H., Neri D., Ballmer-Hofer K., Klemenz R., Schwendener R.A. Cytotoxic targeting of F9 teratocarcinoma tumors with anti-ED-B fibronectin scFv antibody modified liposomes. Br J Cancer. 87:2002;106-112.
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(2002)
Br J Cancer
, vol.87
, pp. 106-112
-
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Marty, C.1
Odermatt, B.2
Schott, H.3
Neri, D.4
Ballmer-Hofer, K.5
Klemenz, R.6
Schwendener, R.A.7
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40
-
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0037178791
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Lack of fucose on human IgG1 N-linked oligosaccharide improves binding to human FcγRIII and antibody-dependent cellular toxicity
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Alteration of the normal carbohydrate on human IgG1 via removal of the fucose moiety (see Figure 2) resulted in an up to 50-fold improvement in binding to human FcγRIII receptor and enhanced in vitro ADCC. This has the potential to increase the therapeutic efficacy of antibodies that utilize the immune system to kill tumor cells.
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Shields R.L., Lai J., Keck R., O'Connell L.Y., Hong K., Meng Y.G., Weikert S.H.A., Presta L.G. Lack of fucose on human IgG1 N-linked oligosaccharide improves binding to human FcγRIII and antibody-dependent cellular toxicity. J Biol Chem. 277:2002;26733-26740 Alteration of the normal carbohydrate on human IgG1 via removal of the fucose moiety (see Figure 2) resulted in an up to 50-fold improvement in binding to human FcγRIII receptor and enhanced in vitro ADCC. This has the potential to increase the therapeutic efficacy of antibodies that utilize the immune system to kill tumor cells.
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(2002)
J Biol Chem
, vol.277
, pp. 26733-26740
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-
Shields, R.L.1
Lai, J.2
Keck, R.3
O'Connell, L.Y.4
Hong, K.5
Meng, Y.G.6
Weikert, S.H.A.7
Presta, L.G.8
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41
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0037474276
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The absence of fucose but not the presence of galactose or bisecting N-acetylglucosamine of human IgG1 complex-type oligosaccharides shows the critical role of enhancing antibody-dependent cellular cytotoxicity
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Previous studies had shown that presence of bisecting N-acetylglucosamine (in effect, introducing a third arm on the normally two-arm carbohydrate) increased ADCC. This study shows that absence of fucose on IgG carbohydrate potentiates ADCC more so than presence of bisecting N-acetylglucosamine.
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Shinkawa T., Nakamura K., Yamane N., Shoji-Hosaka E., Kanda Y., Sakurada M., Uchida K., Anazawa H., Satoh M., Yamasaki M.et al. The absence of fucose but not the presence of galactose or bisecting N-acetylglucosamine of human IgG1 complex-type oligosaccharides shows the critical role of enhancing antibody-dependent cellular cytotoxicity. J Biol Chem. 278:2003;3466-3473 Previous studies had shown that presence of bisecting N-acetylglucosamine (in effect, introducing a third arm on the normally two-arm carbohydrate) increased ADCC. This study shows that absence of fucose on IgG carbohydrate potentiates ADCC more so than presence of bisecting N-acetylglucosamine.
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(2003)
J Biol Chem
, vol.278
, pp. 3466-3473
-
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Shinkawa, T.1
Nakamura, K.2
Yamane, N.3
Shoji-Hosaka, E.4
Kanda, Y.5
Sakurada, M.6
Uchida, K.7
Anazawa, H.8
Satoh, M.9
Yamasaki, M.10
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42
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0035794194
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High resolution mapping of the binding site on human IgG1 for FcγRI, FcγRII, FcγRIII, and the FcRn and design of IgG1 variants with improved binding to the FcγR
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The mapping of residues in human IgG1 involved in binding to human FcγR and FcRn also uncovered specific residues in IgG1 that can be altered to effect improved binding to these receptors. The improved binding translated into enhanced in vitro ADCC.
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Shields R.L., Namenuk A.K., Hong K., Meng Y.G., Rae J., Briggs J., Xie D., Lai J., Stadlen A., Li B.et al. High resolution mapping of the binding site on human IgG1 for FcγRI, FcγRII, FcγRIII, and the FcRn and design of IgG1 variants with improved binding to the FcγR. J Biol Chem. 276:2001;6591-6604 The mapping of residues in human IgG1 involved in binding to human FcγR and FcRn also uncovered specific residues in IgG1 that can be altered to effect improved binding to these receptors. The improved binding translated into enhanced in vitro ADCC.
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(2001)
J Biol Chem
, vol.276
, pp. 6591-6604
-
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Shields, R.L.1
Namenuk, A.K.2
Hong, K.3
Meng, Y.G.4
Rae, J.5
Briggs, J.6
Xie, D.7
Lai, J.8
Stadlen, A.9
Li, B.10
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43
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0035827222
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Molecular basis for immune complex recognition: A comparison of Fc-receptor structures
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Sondermann P., Kaiser J., Jacob U. Molecular basis for immune complex recognition: a comparison of Fc-receptor structures. J Mol Biol. 309:2001;737-749.
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(2001)
J Mol Biol
, vol.309
, pp. 737-749
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Sondermann, P.1
Kaiser, J.2
Jacob, U.3
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44
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0036464719
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Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcγRIIIA gene
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The authors demonstrate the correlation of the FcγRIIIA(F158/V158) polymorphism status of patients and their response to rituximab, an approved anti-CD20 antibody for non-Hodgkin's lymphoma. Patients with the V158 polymorphic form responded better than those with the F158 form.
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Cartron G., Dacheux L., Salles G., Solal-Celigny P., Bardos P., Colombat P., Watier H. Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcγRIIIA gene. Blood. 99:2002;754-758 The authors demonstrate the correlation of the FcγRIIIA(F158/V158) polymorphism status of patients and their response to rituximab, an approved anti-CD20 antibody for non-Hodgkin's lymphoma. Patients with the V158 polymorphic form responded better than those with the F158 form.
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(2002)
Blood
, vol.99
, pp. 754-758
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Cartron, G.1
Dacheux, L.2
Salles, G.3
Solal-Celigny, P.4
Bardos, P.5
Colombat, P.6
Watier, H.7
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45
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0037289807
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The relationship of FcgRIIIA genotype to degree of B cell depletion by rituximab in the treatment of systemic lupus erythematosus
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Anolik J.H., Campbell D., Felgar R.E., Young F., Sanz I., Rosenblatt J., Looney R.J. The relationship of FcgRIIIA genotype to degree of B cell depletion by rituximab in the treatment of systemic lupus erythematosus. Arthritis Rheum. 48:2003;455-459.
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(2003)
Arthritis Rheum
, vol.48
, pp. 455-459
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-
Anolik, J.H.1
Campbell, D.2
Felgar, R.E.3
Young, F.4
Sanz, I.5
Rosenblatt, J.6
Looney, R.J.7
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46
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0035012654
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Crystal structure at 2.8Å of an FcRn/heterodimeric Fc complex: Mechanism of pH-dependent binding
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This crystal structure reveals conformational changes in the IgG Fc, as well as the residues that are involved in the pH-dependent binding of IgG to FcRn. The complex can be used to design IgG with improved binding to FcRn, thereby providing potentially longer-lived therapeutic antibodies.
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Martin W.L., West A.P. Jr., Gan L., Bjorkman P.J. Crystal structure at 2.8Å of an FcRn/heterodimeric Fc complex: mechanism of pH-dependent binding. Mol Cell. 7:2001;867-877 This crystal structure reveals conformational changes in the IgG Fc, as well as the residues that are involved in the pH-dependent binding of IgG to FcRn. The complex can be used to design IgG with improved binding to FcRn, thereby providing potentially longer-lived therapeutic antibodies.
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(2001)
Mol Cell
, vol.7
, pp. 867-877
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Martin, W.L.1
West A.P., Jr.2
Gan, L.3
Bjorkman, P.J.4
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47
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0037325779
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Evidence to support the cellular mechanism involved in serum IgG homeostasis in humans
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Analysis of the intracellular processing of normal and mutated (non-FcRn-binding) human IgG in endothelial cells provides greater understanding of the role of FcRn in controlling the clearance rate of therapeutic antibodies.
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Ward E.S., Zhou J., Ghetie V., Ober R.J. Evidence to support the cellular mechanism involved in serum IgG homeostasis in humans. Int Immunol. 15:2003;187-195 Analysis of the intracellular processing of normal and mutated (non-FcRn-binding) human IgG in endothelial cells provides greater understanding of the role of FcRn in controlling the clearance rate of therapeutic antibodies.
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(2003)
Int Immunol
, vol.15
, pp. 187-195
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Ward, E.S.1
Zhou, J.2
Ghetie, V.3
Ober, R.J.4
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48
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0034879134
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The MHC class I-related receptor, FcRn, plays an essential role in the maternofetal transfer of gamma-globulin in humans
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Firan M., Bawdon R., Radu C., Ober R.J., Eaken D., Antohe F., Ghetie V., Ward E.S. The MHC class I-related receptor, FcRn, plays an essential role in the maternofetal transfer of gamma-globulin in humans. Int Immunol. 13:2001;993-1002.
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(2001)
Int Immunol
, vol.13
, pp. 993-1002
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Firan, M.1
Bawdon, R.2
Radu, C.3
Ober, R.J.4
Eaken, D.5
Antohe, F.6
Ghetie, V.7
Ward, E.S.8
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49
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0037025895
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Receptor-mediated immunoglobulin G transport across mucosal barriers in adult life: Functional expression of FcRn in the mammalian lung
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Spiekermann G.M., Finn P.W., Ward E.S., Dumont J., Dickinson B.L., Blumberg R.S., Lencer W.I. Receptor-mediated immunoglobulin G transport across mucosal barriers in adult life: functional expression of FcRn in the mammalian lung. J Exp Med. 196:2002;303-310.
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(2002)
J Exp Med
, vol.196
, pp. 303-310
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Spiekermann, G.M.1
Finn, P.W.2
Ward, E.S.3
Dumont, J.4
Dickinson, B.L.5
Blumberg, R.S.6
Lencer, W.I.7
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50
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0034042660
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Multiple roles for the major histocompatibility complex class I related receptor FcRn
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Ghetie V., Ward E.S. Multiple roles for the major histocompatibility complex class I related receptor FcRn. Annu Rev Immunol. 18:2000;739-766.
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(2000)
Annu Rev Immunol
, vol.18
, pp. 739-766
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Ghetie, V.1
Ward, E.S.2
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51
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0036839457
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Increasing the affinity of a human IgG1 for the neonatal Fc receptor: Biological consequences
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The pH-dependent binding of IgG to FcRn is an integral part of the current hypothesis on how FcRn influences the serum persistence of IgG. This study shows that increasing the affinity of IgG for FcRn at both pH 6.0 and pH 7.4 results in decreased half-life, providing support for the accepted mechanism.
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Dall'Acqua W.F., Woods R.M., Ward E.S., Palaszynski S.R., Patel N.K., Brewah Y.A., Wu H., Keiner P.A., Langermann S. Increasing the affinity of a human IgG1 for the neonatal Fc receptor: biological consequences. J Immunol. 169:2002;5171-5180 The pH-dependent binding of IgG to FcRn is an integral part of the current hypothesis on how FcRn influences the serum persistence of IgG. This study shows that increasing the affinity of IgG for FcRn at both pH 6.0 and pH 7.4 results in decreased half-life, providing support for the accepted mechanism.
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(2002)
J Immunol
, vol.169
, pp. 5171-5180
-
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Dall'Acqua, W.F.1
Woods, R.M.2
Ward, E.S.3
Palaszynski, S.R.4
Patel, N.K.5
Brewah, Y.A.6
Wu, H.7
Keiner, P.A.8
Langermann, S.9
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52
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0036079202
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Expression of the neonatal Fc receptor (FcRn) at the blood-brain barrier
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Schlachetzki F., Zhu C., Pardridge W.M. Expression of the neonatal Fc receptor (FcRn) at the blood-brain barrier. J Neurochem. 81:2002;203-206.
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(2002)
J Neurochem
, vol.81
, pp. 203-206
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Schlachetzki, F.1
Zhu, C.2
Pardridge, W.M.3
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53
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0034718510
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Antibodies have the intrinsic capacity to destroy antigens
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Wentworth A.D., Jones L.H., Wentworth P. Jr., Janda K.D., Lerner R.A. Antibodies have the intrinsic capacity to destroy antigens. Proc Natl Acad Sci USA. 97:2000;10930-10935.
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(2000)
Proc Natl Acad Sci USA
, vol.97
, pp. 10930-10935
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Wentworth, A.D.1
Jones, L.H.2
Wentworth P., Jr.3
Janda, K.D.4
Lerner, R.A.5
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54
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0035823071
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Antibody catalysis of the oxidation of water
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Wentworth P. Jr., Jones L.H., Wentworth A.D., Zhu X., Larsen N.A., Wilson I.A., Xu X., Goddard W.A. III, Janda K.D., Eschenmoser A., Lerner R.A. Antibody catalysis of the oxidation of water. Science. 293:2001;1806-1811.
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(2001)
Science
, vol.293
, pp. 1806-1811
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Wentworth P., Jr.1
Jones, L.H.2
Wentworth, A.D.3
Zhu, X.4
Larsen, N.A.5
Wilson, I.A.6
Xu, X.7
Goddard W.A. III8
Janda, K.D.9
Eschenmoser, A.10
Lerner, R.A.11
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55
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0037022643
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Mechanism for antibody catalysis of the oxidation of water by singlet dioxygen
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Datta D., Vaidehi N., Xu X., Goddard W.A. III Mechanism for antibody catalysis of the oxidation of water by singlet dioxygen. Proc Natl Acad Sci USA. 99:2002;2636-2641.
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(2002)
Proc Natl Acad Sci USA
, vol.99
, pp. 2636-2641
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Datta, D.1
Vaidehi, N.2
Xu, X.3
Goddard W.A. III4
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56
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0037073888
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Evidence for antibody-catalyzed ozone formation in bacterial killing and inflammation
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Fourth in a series of papers, this study shows that antibodies can catalyze the conversion of singlet molecular oxygen to hydrogen peroxide and ozone, a newly discovered effector function of antibodies, and effect killing of bacteria.
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Wentworth P. Jr., McDunn J.E., Wentworth A.D., Takeuchi C., Nieva J., Jones T., Bautista C., Ruedi J.M., Gutierrez A., Janda K.D.et al. Evidence for antibody-catalyzed ozone formation in bacterial killing and inflammation. Science. 298:2002;2195-2199 Fourth in a series of papers, this study shows that antibodies can catalyze the conversion of singlet molecular oxygen to hydrogen peroxide and ozone, a newly discovered effector function of antibodies, and effect killing of bacteria.
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(2002)
Science
, vol.298
, pp. 2195-2199
-
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Wentworth P., Jr.1
McDunn, J.E.2
Wentworth, A.D.3
Takeuchi, C.4
Nieva, J.5
Jones, T.6
Bautista, C.7
Ruedi, J.M.8
Gutierrez, A.9
Janda, K.D.10
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57
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0037453048
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Investigating antibody-catalyzed ozone generation by human neutrophils
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Babior B.M., Takeuchi C., Ruedi J., Gutierrez A., Wentworth P. Jr. Investigating antibody-catalyzed ozone generation by human neutrophils. Proc Natl Acad Sci USA. 100:2003;3031-3034.
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(2003)
Proc Natl Acad Sci USA
, vol.100
, pp. 3031-3034
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Babior, B.M.1
Takeuchi, C.2
Ruedi, J.3
Gutierrez, A.4
Wentworth P., Jr.5
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58
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0037452678
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Evidence for the production of trioxygen species during antibody-catalyzed chemical modification of antigens
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Further studies of the ability of antibodies to catalyze the production of ozone, including elucidation of a specific tryptophan in the constant light domain that may be involved.
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Wentworth P. Jr., Wentworth A.D., Zhu X., Wilson I.A., Janda K.D., Eschenmoser A., Lerner R.A. Evidence for the production of trioxygen species during antibody-catalyzed chemical modification of antigens. Proc Natl Acad Sci USA. 100:2003;1490-1493 Further studies of the ability of antibodies to catalyze the production of ozone, including elucidation of a specific tryptophan in the constant light domain that may be involved.
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(2003)
Proc Natl Acad Sci USA
, vol.100
, pp. 1490-1493
-
-
Wentworth P., Jr.1
Wentworth, A.D.2
Zhu, X.3
Wilson, I.A.4
Janda, K.D.5
Eschenmoser, A.6
Lerner, R.A.7
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59
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0035823022
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Complement-independent, peroxide-induced antibody lysis of platelets in HIV-1 related immune thrombocytopenia
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This study shows the effect of antibody-generated hydrogen peroxide on platelet lysis. It also suggests that antibodies against specific cellular targets (in this case, the integrin GPIIIa) may invoke an intracellular mechanism for singlet molecular oxygen generation and subsequent deleterious effect of generated peroxide (or other oxygen species).
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Nardi M., Tomlinson S., Greco M.A., Karpatkin S. Complement-independent, peroxide-induced antibody lysis of platelets in HIV-1 related immune thrombocytopenia. Cell. 106:2001;551-561 This study shows the effect of antibody-generated hydrogen peroxide on platelet lysis. It also suggests that antibodies against specific cellular targets (in this case, the integrin GPIIIa) may invoke an intracellular mechanism for singlet molecular oxygen generation and subsequent deleterious effect of generated peroxide (or other oxygen species).
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(2001)
Cell
, vol.106
, pp. 551-561
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Nardi, M.1
Tomlinson, S.2
Greco, M.A.3
Karpatkin, S.4
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60
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0035874887
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High affinity restricts the localization and tumor penetration of single-chain Fv antibody molecules
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An elegant study showing that increased antibody affinity may not always be optimal for the delivery of tumor-infiltrating antibodies.
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Adams G.P., Schler R., McCall A.M., Simmons H.H., Horak E.M., Alpaugh R.K., Marks J.D., Weiner L.M. High affinity restricts the localization and tumor penetration of single-chain Fv antibody molecules. Cancer Res. 61:2001;4750-4755 An elegant study showing that increased antibody affinity may not always be optimal for the delivery of tumor-infiltrating antibodies.
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(2001)
Cancer Res
, vol.61
, pp. 4750-4755
-
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Adams, G.P.1
Schler, R.2
McCall, A.M.3
Simmons, H.H.4
Horak, E.M.5
Alpaugh, R.K.6
Marks, J.D.7
Weiner, L.M.8
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61
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0035251638
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Design and application of diabodies, triabodies and tetrabodies for cancer targeting
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Todorovska A., Roovers R.C., Dolezal O., Kortt A.A., Hoogenboom H.R., Hudson P.J. Design and application of diabodies, triabodies and tetrabodies for cancer targeting. J Immunol Methods. 248:2001;47-66.
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(2001)
J Immunol Methods
, vol.248
, pp. 47-66
-
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Todorovska, A.1
Roovers, R.C.2
Dolezal, O.3
Kortt, A.A.4
Hoogenboom, H.R.5
Hudson, P.J.6
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62
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0042754502
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Construction and characterization of minibodies for imaging and therapy of colorectal carcinomas
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Yazaki P.J., Wu A.M. Construction and characterization of minibodies for imaging and therapy of colorectal carcinomas. Methods Mol Biol. 207:2003;351-364.
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(2003)
Methods Mol Biol
, vol.207
, pp. 351-364
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Yazaki, P.J.1
Wu, A.M.2
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63
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0036796777
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Efficacy of a novel PEGylated humanized anti-TNF fragment (CDP870) in patients with rheumatoid arthritis: A phase II double-blinded, randomized, dose-escalating trial
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Choy E.H.S., Hazleman B., Smith M., Moss K., Lisi L., Scott D.G.I., Patel J., Sopwith M., Isenberg D.A. Efficacy of a novel PEGylated humanized anti-TNF fragment (CDP870) in patients with rheumatoid arthritis: a phase II double-blinded, randomized, dose-escalating trial. Rheumatol. 41:2002;1133-1137.
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(2002)
Rheumatol
, vol.41
, pp. 1133-1137
-
-
Choy, E.H.S.1
Hazleman, B.2
Smith, M.3
Moss, K.4
Lisi, L.5
Scott, D.G.I.6
Patel, J.7
Sopwith, M.8
Isenberg, D.A.9
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64
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0037144397
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Albumin binding as a general strategy for improving the pharmacokinetics of proteins
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Dennis M.S., Zhang M., Meng Y.G., Radkhodayan M., Kirchhofer D., Combs D., Damico L.A. Albumin binding as a general strategy for improving the pharmacokinetics of proteins. J Biol Chem. 277:2002;35035-35043.
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(2002)
J Biol Chem
, vol.277
, pp. 35035-35043
-
-
Dennis, M.S.1
Zhang, M.2
Meng, Y.G.3
Radkhodayan, M.4
Kirchhofer, D.5
Combs, D.6
Damico, L.A.7
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