Anti-CD40 monoclonal antibody

Leukemia and Lymphoma

Volumn 46, Issue 8, 2005, Pages 1105-1113

  Geldart, Tom ^a   Illidge, Tim ^b  

^a SOUTHAMPTON GENERAL HOSPITAL   (United Kingdom)

^b UNIVERSITY OF MANCHESTER   (United Kingdom)

Author keywords

Anti CD40; Immunotherapy; Monoclonal antibody; Novel treatment; Therapy

Indexed keywords

ADENOVIRUS VECTOR; ALEMTUZUMAB; CD40 ANTIGEN; CD40 LIGAND; CD40 LIGAND MONOCLONAL ANTIBODY; INTERLEUKIN 2; RITUXIMAB; TRASTUZUMAB; LIGAND; MONOCLONAL ANTIBODY;

AMINOTRANSFERASE BLOOD LEVEL; ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; ANTIGEN EXPRESSION; ANTINEOPLASTIC ACTIVITY; ATHEROSCLEROSIS; AUTOIMMUNE DISEASE; CANCER CELL; CARCINOMA; CELL BASED GENE THERAPY; CELL MEDIATED CYTOTOXICITY; CELL PROLIFERATION; CELLULAR IMMUNITY; CLINICAL TRIAL; COMPLEMENT DEPENDENT CYTOTOXICITY; CYTOTOXIC T LYMPHOCYTE; DEGENERATIVE DISEASE; DRUG MECHANISM; DRUG TARGETING; ENZYME DEFECT; GENE DELIVERY SYSTEM; GRAFT REJECTION; HEMATOLOGIC MALIGNANCY; HUMAN; HUMORAL IMMUNITY; INSULIN DEPENDENT DIABETES MELLITUS; MOLECULAR INTERACTION; NONHUMAN; PRIORITY JOURNAL; REVIEW; RHEUMATOID ARTHRITIS; SYSTEMIC LUPUS ERYTHEMATOSUS; T LYMPHOCYTE; VIRAL GENE THERAPY; BIOLOGICAL MODEL; GENETICS; IMMUNOLOGY; IMMUNOTHERAPY; NEOPLASM; SIGNAL TRANSDUCTION;

ANTIBODIES, MONOCLONAL; ANTIGENS, CD40; CD40 LIGAND; HUMANS; IMMUNOTHERAPY; LIGANDS; MODELS, IMMUNOLOGICAL; NEOPLASMS; SIGNAL TRANSDUCTION;

EID: 23144463732     PISSN: 10428194     EISSN: None     Source Type: Journal    
DOI: 10.1080/10428190500085255     Document Type: Review

References (95)

1. Paulie S, Ehlin-Henriksson B, Mellstedt H, Koho H, Ben-Aissa H, Perlmann P. A p50 surface antigen restricted to human urinary bladder carcinomas and B lymphocytes. Cancer Immunol Immunother 1985;20(1):23-28.
2. van Kooten C, Banchereau J. CD40-CD40 ligand. J Leukoc Biol 2000;67(1):2-17.
3. Grewal IS, Flavell RA. CD40 and CD154 in cell-mediated immunity. Annu Rev Immunol 1998;16:111-135.
4. Funakoshi S, Longo DL, Beckwith M, Conley DK, Tsarfaty G, Tsarfaty I et al. Inhibition of human B-cell lymphoma growth by CD40 stimulation. Blood 1994;83(10):2787-2794.
5. Hayashi T, Treon SP, Hideshima T, Tai Y-T, Akiyama M, Richardson P et al. Recombinant humanized anti-CD40 monoclonal antibody triggers autologous antibody-dependent cell-mediated cytotoxicity against multiple mycloma cells. Br J Haematol 2003;121(4):592-596.
6. Young LS, Eliopoulos AG, Gallagher NJ, Dawson CW. CD40 and epithelial cells: across the great divide. Immunol Today 1998;19(11):502-506.
7. Alexandroff AB, Jackson AM, Paterson T, Haley JL, Ross JA, Longo DL et al. Role for CD40-CD40 ligand interactions in the immune response to solid tumours. Mol Immunol 2000;37(9):515-526.
8. Wingett DG, Vestal RE, Forcier K, Hadjokas N, Nielson CP. CD40 is functionally expressed on human breast carcinomas: variable inducibility by cytokines and enhancement of Fas-mediated apoptosis. Breast Cancer Res Treat 1998;50(1):27-36.
9. Sabel MS, Yamada M, Kawaguchi Y, Chen FA, Takita H, Bankert RB. CD40 expression on human lung cancer correlates with metastatic spread. Cancer Immunol Immunother 2000;49(2):101-108.
10. Gallagher NJ, Eliopoulos AG, Agathangelo A, Oates J, Crocker J, Young LS. CD40 activation in epithelial ovarian carcinoma cells modulates growth, apoptosis, and cytokine secretion. Mol Pathol 2002;55(2):110-120.
11. Cooke PW, James ND, Ganesan R, Wallace M, Burton A, Young LS. CD40 expression in bladder cancer. J Pathol 1999;188(1):38-43.
12. Thomas WD, Smith MJ, Si Z, Hersey P. Expression of the costimulatory molecule CD40 on melanoma cells. Int J Cancer 1996;68(6):795-801.
13. Biancone L, Cantaluppi V, Camussi G. CD40-CD154 interaction in experimental and human disease (review). Int J Mol Med 1999;3(4):343-353.
14. von Leoprechting A, van der Bruggen P, Pahl HL, Aruffo A, Simon JC. Stimulation of CD40 on immunogenic human malignant melanomas augments their cytotoxic T lymphocyte-mediated lysis and induces apoptosis. Cancer Res 1999;59(6):1287-1294.
15. Stamenkovic I, Clark EA, Seed B. A B-lymphocyte activation molecule related to the nerve growth factor receptor and induced by cytokines in carcinomas. Embo J 1989;8(5):1403-1410.
16. Karpusas M, Hsu YM, Wang JH, Thompson J, Lederman S, Chess L et al. A crystal structure of an extracellular fragment of human CD40 ligand. Structure 1995;3(12):1426.
17. Yellin MJ, Lee JJ, Chess L, Lederman S. A human CD4-T cell leukemia subclone with contact-dependent helper function. J Immunol 1991;147(10):3389-3395.
18. Lederman S, Yellin MJ, Krichevsky A, Belko J, Lee JJ, Chess L. Identification of a novel surface protein on activated CD4 + T cells that induces contact-dependent B cell differentiation (help). J Exp Med 1992;175(4):1091-1101.
19. Armitage RJ, Sato TA, Macduff BM, Clifford KN, Alpert AR, Smith CA et al. Identification of a source of biologically active CD40 ligand. Eur J Immunol 1992;22(8):2071-2076.
20. Gauchat JF, Henchoz S, Fattah D, Mazzei G, Aubry JP, Jomotte T et al. CD40 ligand is functionally expressed on human eosinophils. Eur J Immunol 1995;25(3):863-865.
21. Henn V, Slupsky JR, Grafe M, Anagnostopoulos I, Forster R, Muller-Berghaus G et al. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature 1998;391(6667):591-594.
22. Gauchat JF, Henchoz S, Mazzei G, Aubry JP, Brunner T, Blasey H et al. Induction of human IgE synthesis in B cells by mast cells and basophils. Nature 1993;365(6444):340-343.
23. Lederman S, Yellin MJ, Inghirami G, Lee JJ, Knowles DM, Chess L. Molecular interactions mediating T-B lymphocyte collaboration in human lymphoid follicles. Roles of T cell-B-cell-activating molecule (5c8 antigen) and CD40 in contact-dependent help. J Immunol 1992;149(12):3817-3826.
24. Hollenbaugh D, Grosmaire LS, Kullas CD, Chalupny NJ, Braesch-Andersen S, Noelle RJ et al. The human T cell antigen gp39, a member of the TNF gene family, is a ligand for the CD40 receptor: expression of a soluble form of gp39 with B cell co-stimulatory activity. Embo J 1992;11(12):4313-4321.
25. Spriggs MK, Armitage RJ, Strockbine L, Clifford KN, Macduff BM, Sato TA et al. Recombinant human CD40 ligand stimulates B cell proliferation and immunoglobulin E secretion. J Exp Med 1992;176(6):1543-1550.
26. Villa A, Notarangelo LD, Di Santo JP, Macchi PP, Strina D, Frattini A et al. Organization of the human CD40L gene: implications for molecular defects in X chromosome-linked hyper-IgM syndrome and prenatal diagnosis. Proc Natl Acad Sci USA 1994;91(6):2110-2114.
27. Graf D, Muller S, Korthauer U, van Kooten C, Weise C, Kroczek RA. A soluble form of TRAP (CD40 ligand) is rapidly released after T cell activation. Eur J Immunol 1995;25(6):1749-1754.
28. Mazzei GJ, Edgerton MD, Losberger C, Lecoanet-Henchoz S, Graber P, Durandy A et al. Recombinant soluble trimeric CD40 ligand is biologically active. J Biol Chem 1995;270(13):7025-7028.
29. Uckun FM, Gajl-Peczalska K, Myers DE, Jaszcz W, Haissig S, Ledbetter JA. Temporal association of CD40 antigen expression with discrete stages of human B-cell ontogeny and the efficacy of anti-CD40 immunotoxins against clonogenic B-lineage acute lymphoblastic leukemia as well as B-lineage non-Hodgkin's lymphoma cells. Blood 1990;76(12):2449-2456.
30. Yellin MJ, Sinning J, Covey LR, Sherman W, Lee JJ, Glickman-Nir E et al. T lymphocyte T cell-B cell-activating molecule/CD40-L molecules induce normal B cells or chronic lymphocytic leukemia B cells to express CD80 (B7/BB-1) and enhance their costimulatory activity. j Immunol 1994;153(2):666-674.
31. Ranheim EA, Kipps TJ. Activated T cells induce expression of B7/BB1 on normal or leukemic B cells through a CD40-dependent signal. J Exp Med 1993;177(4):925-935.
32. Schattner EJ, Elkon KB, Yoo DH, Tumang J, Krammer PH, Crow MK et al. CD40 ligation induces Apo-1/Fas expression on human B lymphocytes and facilitates apoptosis through the Apo-1/Fas pathway. J Exp Med 1995;182(5):1557-1565.
33. Lederman S, Yellin MJ, Cleary AM, Pernis A, Inghirami G, Cohn LE et al. T-BAM/CD40-L on helper T lymphocytes augments lymphokine-induced B cell Ig isotype switch recombination and rescues B cells from programmed cell death. J Immunol 1994;152(5):2163-2171.
34. Cleary AM, Fortune SM, Yellin MJ, Chess L, Lederman S. Opposing roles of CD95 (Fas/APO-1) and CD40 in the death and rescue of human low density tonsillar B cells. J Immunol 1995;155(7):3329-3337.
35. Tsubata T, Wu J, Honjo T. B-cell apoptosis induced by antigen receptor crosslinking is blocked by a T-cell signal through CD40. Nature 1993;364(6438):645-648.
36. Lederman S, Cleary AM, Yellin MJ, Frank DM, Karpusas M, Thomas DW et al. The central role of the CD40-ligand and CD40 pathway in T-lymphocyte-mediated differentiation of B lymphocytes. Curr Opin Hematol 1996;3(1):77-86.
37. Noelle RJ, Ledbetter JA, Aruffo A. CD40 and its ligand, an essential ligand-receptor pair for thymus-dependent B-cell activation. Immunol Today 1992;13(11):431-433.
38. Aruffo A, Farrington M, Hollenbaugh D, Li X, Milatovich A, Nonoyama S et al. The CD40 ligand, gp39, is defective in activated T cells from patients with X-linked hyper-IgM. syndrome. Cell 1993;72(2):291-300.
39. Aruffo A, Hollenbaugh D, Wu LH, Ochs HD. The molecular basis of X-linked agammaglobulinemia, hyper-IgM syndrome, and severe combined immunodeficiency in humans. Curr Opin Hematol 1994;1(1):12-18.
40. Caux C, Massacrier C, Vanbervliet B, Dubois B, Van Kooten C, Durand I et al. Activation of human dendritic cells through CD40 cross-linking. J Exp Med 1994;180(4):1263-1272.
41. Peng X, Remacle JE, Kasran A, Huylebroeck D, Ceuppens JL. IL-12 up-regulates CD40 ligand (CD154) expression on human T cells. J Immunol 1998;160(3):1166-1172.
42. Ridge JP, Di Rosa F, Matzinger P. A conditioned dendritic cell can be a temporal bridge between a CD4 + T-helper and a T-killer cell. Nature 1998;393(6684):474-478.
43. Bennett SR, Carbone FR, Karamalis F, Flavell RA, Miller JF, Heath WR. Help for cytotoxic-T-cell responses is mediated by CD40 signalling. Nature 1998;393(6684):478-480.
44. Schoenberger SP, Toes RE, van der Voort EI, Offiinga R, Melief CJ. T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions. Nature 1998;393(6684): 480-483.
45. Arch RH, Gedrich RW, Thompson CB. Tumor necrosis factor receptor-associated factors (TRAFs) - a family of adapter proteins that regulates life and death. Genes Dev 1998;12(18):2821-2830.
46. Pullen SS, Dang TT, Crute JJ, Kehry MR. CD40 signaling through tumor necrosis factor receptor-associated factors (TRAFs). Binding site specificity and activation of down-stream pathways by distinct TRAFs. J Biol Chem 1999;274(20):14246-14254.
47. Ren CL, Morio T, Fu SM, Geha RS. Signal transduction via CD40 involves activation of lyn kinase and phosphatidylinositol-3-kinase, and phosphorylation of phospholipase C gamina 2. J Exp Med 1994;179(2):673-680.
48. Ren CL, Fu SM, Geha RS. Protein tyrosine kinase activation and protein kinase C translocation are functional components of CD40 signal transduction in resting human B cells. Immunol Invest 1994;23(6-7):437-448.
49. Davies CC, Mason J, Wakelam MJ, Young LS, Eliopoulos AG. Inhibition of phosphatidylinositol 3-kinase- and ERK MAPK-regulated protein synthesis reveals the pro-apoptotic properties of CD40 ligation in carcinoma cells. J Biol Chem 2004;279(2):1010-1019.
50. Tsukamoto N, Kobayashi N, Azuma S, Yamamoto T, Inoue J. Two differently regulated nuclear factor kappaB activation pathways triggered by the cytoplasmic tail of CD40. Proc Natl Acad Sci USA 1999;96(4):1234-1239.
51. Young LS, Dawson CW, Brown KW, Rickinson AB. Identification of a human epithelial cell surface protein sharing an epitope with the C3d/Epstein-Barr virus receptor molecule of B lymphocytes. Int J Cancer 1989;43(5):786-794.
52. van Kooten C, Banchereau J. Functional role of CD40 and its ligand. Int Arch Allergy Immunol 1997; 113(4):393-399.
53. Singh SR, Casper K, Summers S, Swerlick RA. CD40 expression and function on human dermal microvascular endothelial cells: role in cutaneous inflammation. Clin Exp Dermatol 2001;26(5):434-440.
54. Gormand F, Briere F, Peyrol S, Raccurt M, Durand I, Ait-Yahia S et al. CD40 expression by human bronchial epithelial cells. Scand J Immunol 1999;49(4):355-361.
55. Yellin MJ, D'Agati V, Parkinson G, Han AS, Szema A, Baum D et al. Immunohistologic analysis of renal CD40 and CD40L expression in lupus nephritis and other glomerulonephritides. Arthritis Rheum 1997;40(1):124-134.
56. Galy AH, Spits H. CD40 is functionally expressed on human thymic epithelial cells. J Immunol 1992;149(3):775-782.
57. Iwata M, Soya K, Sawa M, Sakimoto T, Hwang DG. CD40 expression in normal human cornea and regulation of CD40 in cultured human corneal epithelial and stromal cells. Invest Ophthalmol Vis Sci 2002;43(2):348-357.
58. Agathanggelou A, Niedobitek G, Chen R, Nicholls J, Yin W, Young LS. Expression of immune regulatory molecules in Epstein-Barr virus-associated nasopharyngeal carcinomas with prominent lymphoid stroma. Evidence for a functional interaction between epithelial tumor cells and infiltrating lymphoid cells. Am J Pathol 1995;147(4):1152-1160.
59. Hess S, Engelmann H. A novel function of CD40: induction of cell death in transformed cells. J Exp Med 1996;183(1):159-167.
60. Eliopoulos AG, Dawson CW, Mosialos G, Floettmann JE, Rowe M, Armitage RJ et al. CD40-induced growth inhibition in epithelial cells is mimicked by Epstein-Barr virus-encoded LMP1: involvement of TRAF3 as a common mediator. Oncogene 1996;13(10):2243-2254.
61. Eliopoulos AG, Davies C, Knox PG, Gallagher NJ, Afford SC, Adams DH et al. CD40 induces apoptosis in carcinoma cells through activation of cytotoxic ligands of the tumor necrosis factor superfamily. Mol Cell Biol 2000;20(15):5503-5515.
62. Szocinski JL, Khaled AR, Hixon J, Halverson D, Funakoshi S, Fanslow WC et al. Activation-induced cell death of aggressive histology lymphomas by CD40 stimulation: induction of bax. Blood 2002;100(1):217-223.
63. Hirano A, Longo DL, Taub DD, Ferris DK, Young LS, Eliopoulos AG et al. Inhibition of human breast carcinoma growth by a soluble recombinant human CD40 ligand. Blood 1999;93(9):2999-3007.
64. Bugajska U, Georgopoulos NT, Southgate J, Johnson PW, Graber P, Gordon J et al. The effects of malignant transformation on susceptibility of human urothelial cells to CD40-mediated apoptosis. J Natl Cancer Inst 2002;94(18):1381-1395.
65. Tong AW, Papayoti MH, Netto G, Armstrong DT, Ordonez G, Lawson JM et al. Growth-inhibitory effects of CD40 ligand (CD154) and its endogenous expression in human breast cancer. Clin Cancer Res 2001;7(3):691-703.
66. Ghamande S, Hylander BL, Oflazoglu E, Lele S, Fanslow W, Repasky EA. Recombinant CD40 ligand therapy has significant antitumor effects on CD40-positive ovarian tumor xenografts grown in SCID mice and demonstrates an augmented effect with cisplatin. Cancer Res 2001;61(20):7556-7562.
67. Posner MR, Cavacini LA, Upton MP, Tillman KC, Gornstein ER, Norris CM Jr. Surface membrane-expressed CD40 is present on tumor cells from squamous cell cancer of the head and neck in vitro and in vivo and regulates cell growth in tumor cell lines. Clin Cancer Res 1999;5(8):2261-2270.
68. Marches R, Racila E, Tucker TF, Picker L, Mongini P, Hsueh R et al. Tumour dormancy and cell signalling - III: Role of hypercrosslinking of IgM and CD40 on the induction of cell cycle arrest and apoptosis in B lymphoma cells. Ther Immunol 1995;2(3):125-136.
69. Reff ME, Carner K, Chambers KS, Chinn PC, Leonard JE, Raab R et al. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood 1994,83(2):435-445.
70. Shan D, Ledbetter JA, Press OW. Apoptosis of malignant human B cells by ligation of CD20 with monoclonal antibodies. Blood 1998;91(5):1644-1652.
71. Cragg MS, Morgan SM, Chan HT, Morgan BP, Filatov AV, Johnson PW et al. Complement-mediated lysis by ami-CD20 mAb correlates with segregation into lipid rafts. Blood 2003;101(3):1045-1052.
72. Heit W, Bunjes D, Wiesneth M, Schmeiser T, Arnold R, Hale G et al. Ex vivo T-cell depletion with the monoclonal antibody Campath-1 plus human complement effectively prevents acute graft-versus-host disease in allogeneic bone marrow transplantation. Br J Haematol 1986;64(3):479-486.
73. Dyer MJ, Hale G, Hayhoe FG, Waldmann H. Effects of CAMPATH-1 antibodies in vivo in patients with lymphoid malignancies: influence of antibody isotype. Blood 1989;73(6):1431-1439.
74. Greenwood J, Clark M, Waldmann H. Structural motifs involved in human IgG antibody effector functions. Eur J Immunol 1993;23(5):1098-1104.
75. Shwkowski MX, Lofgren JA, Lewis GD, Hotaling TE, Fendly BM, Fox JA. Nonclinical studies addressing the mechanism of action of trastuzumab (Herceptin). Semin Oncol 1999;26(4 Suppl. 12):60-70.
76. Harries M, Smith I. The development and clinical use of trastuzumab (Herceptin). Endocr Relat Cancer 2002;9(2):75-85.
77. Eliopoulos AG, Young LS. The role of the CD40 pathway in the pathogenesis and treatment of cancer. Curr Opin Pharmacol 2004;4(4):360-367.
78. French RR, Chan HT, Tutt AL, Glennie MJ. CD40 antibody evokes a cytotoxic T-cell response that eradicates lymphoma and bypasses T-cell help. Nat Med 1999;5(5):548-553.
79. Todryk SM, Tutt AL, Green MH, Smallwood JA, Halanek N, Dalgleish AG et al. CD40 ligation for immunotherapy of solid tumours. J Immunol Meth 2001;248(1-2):139-147.
80. Honeychurch J, Glennie MJ, Johnson PW, Illidge TM. Anti-CD40 monoclonal antibody therapy in combination with irradiation results in a CD8 T-cell-dependent immunity to B-cell lymphoma. Blood 2003;102(4):1449-1457.
81. Early GS, Zhao W, Burns CM. Anti-CD40 ligand antibody treatment prevents the development of lupus-like nephritis in a subset of New Zealand black x New Zealand white mice. Response correlates with the absence of an anti-antibody response. J Immunol 1996;157(7):3159-3164.
82. Kitagawa M, Suzuki H, Adachi Y, Nakamura H, Yoshino S, Sumida T. Interferon-gamma enhances interleukin 12 production in rheumatoid synovial cells via CD40-CD154 dependent and independent pathways. J Rheumatol 2001;28(8):1764-1771.
83. Balasa B, Krahl T, Patstone G, Lee J, Tisch R, McDevitt HO et al. CD40 ligand-CD40 interactions are necessary for the initiation of insulitis and diabetes in nonobese diabetic mice. J Immunol 1997;159(9):4620-4627.
84. Mach F, Schonbeck U, Libby P. CD40 signaling in vascular cells: a key role in atherosclerosis? Atherosclerosis 1998;137(Suppl.):S89-S95.
85. Mach F, Schonbeck U, Sukhova GK, Atkinson E, Libby P. Reduction of atherosclerosis in mice by inhibition of CD40 signalling. Nature 1998;394(6689):200-203.
86. Schonbeck U, Mach F, Sukhova GK, Atkinson E, Levesque E, Herman M. et al. Expression of stromelysin-3 in atherosclerotic lesions: regulation via CD40 - CD40 ligand signaling in vitro and in vivo. J Exp Med 1999;189(5):843-853.
87. Lutgens E, Gorelik L, Daemen MJ, de Muinck ED, Grewal IS, Koteliansky VE et al. Requirement for CD154 in the progression of atherosclerosis. Nat Med 1999;5(11):1313-1316.
88. Gerritse K, Laman JD, Noelle RJ, Aruffo A, Ledbetter JA, Boersma WJ et al. CD40-CD40 ligand interactions in experimental allergic encephalomyelitis and multiple sclerosis. Proc Natl Acad Sci USA 1996;93(6):2499-2504.
89. Tan J, Town T, Suo Z, Wu Y, Song S, Kundtz A et al. Induction of CD40 on human endothelial cells by Alzheimer's beta-amyloid peptides. Brain Res Bull 1999;50(2):143-148.
90. Tan J, Town T, Paris D, Mori T, Suo Z, Crawford F et al. Microglial activation resulting from CD40-CD40L interaction after beta-amyloid stimulation. Science 1999;286(5448): 2352-2355.
91. Larsen CP, Alexander DZ, Hollenbaugh D, Elwood ET, Ritchie SC, Aruffo A et al. CD40-gp39 interactions play a critical role during allograft rejection. Suppression of allograft rejection by blockade of the CD40-gp39 pathway. Transplantation 1996;61(1):4-9.
92. Kirk AD, Burkly LC, Batty DS, Baumgartner RE, Berning JD, Buchanan K et al. Treatment with humanized monoclonal antibody against CD154 prevents acute renal allograft rejection in nonhuman primates. Nat Med 1999;5 (6):686-693.
93. Vonderheide RH, Dutcher JP, Anderson JE, Eckhardt SG, Stephans KF, Razvillas B et al. Phase I study of recombinant human CD40 ligand in cancer patients. J Clin Oncol 2001;19(13):3280-3287.
94. Wierda WG, Cantwell MJ, Woods SJ, Rassenti LZ, Prussak CE, Kipps TJ. CD40-ligand (CD154) gene therapy for chronic lymphocytic leukemia. Blood 2000;96(9):2917-2924.
95. Takahashi S, Yotnda P, Rousseau RF, Mei Z, Smith S, Rill D et al. Transgenic expression of CD40L and interleukin-2 induces an autologous antitumor immune response in patients with non-Hodgkin's lymphoma. Cancer Gene Ther 2001;8(5):378-387.