Fifteen years of gene therapy based on chimeric antigen receptors: Are we nearly there yet?

Human Gene Therapy

Volumn 20, Issue 11, 2009, Pages 1229-1239

  Dotti, Gianpietro ^a   Savoldo, Barbara ^a   Brenner, Malcolm ^a  

^a TEXAS CHILDREN S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHIMERIC ANTIBODY; LENTIVIRUS VECTOR; LYMPHOCYTE ANTIGEN RECEPTOR; RETROVIRUS VECTOR; HYBRID PROTEIN;

ANTIGEN SPECIFICITY; CANCER IMMUNOTHERAPY; CANCER INVASION; CELL INTERACTION; CLINICAL TRIAL; CYTOTOXIC T LYMPHOCYTE; GENE THERAPY; GENE TRANSFER; HUMAN; MEMORY CELL; NATURAL KILLER CELL; NONHUMAN; NONVIRAL GENE DELIVERY SYSTEM; PROTEIN EXPRESSION; REVIEW; T LYMPHOCYTE; TUMOR IMMUNITY; VIRAL GENE DELIVERY SYSTEM; BIOLOGICAL MODEL; GENE VECTOR; GENETICS; IMMUNOLOGY; IMMUNOTHERAPY; LENTIVIRINAE; PROCEDURES; RETROVIRUS; TRENDS; TUMOR ESCAPE;

GENE TRANSFER TECHNIQUES; GENETIC THERAPY; GENETIC VECTORS; HUMANS; IMMUNOTHERAPY; LENTIVIRUS; MODELS, IMMUNOLOGICAL; RECEPTORS, ANTIGEN; RECOMBINANT FUSION PROTEINS; RETROVIRIDAE; T-LYMPHOCYTES; TUMOR ESCAPE;

EID: 70449123840     PISSN: 10430342     EISSN: None     Source Type: Journal    
DOI: 10.1089/hum.2009.142     Document Type: Review

References (90)

1. Ahmadzadeh, M., and Rosenberg, S.A. (2006). IL-2 administration increases CD4+ CD25hi Foxp3+ regulatory T cells in cancer patients. Blood 107, 2409-2414.
2. Ahmed, N., Ratnayake, M., Savoldo, B., Perlaky, L., Dotti, G., Wels, W.S., Bhattacharjee, M.B., Gilbertson, R.J., Shine, H.D., Weiss, H.L., Rooney, C.M., Heslop, H.E., and Gottschalk, S. (2007). Regression of experimental medulloblastoma following transfer of HER2-specific T cells. Cancer Res. 67, 5957-5964.
3. Alpdogan, O., Muriglan, S.J., Eng, J.M., Willis, L.M., Greenberg, A.S., Kappel, B.J., and van den Brink, M.R. (2003). IL-7 enhances peripheral T cell reconstitution after allogeneic hematopoietic stem cell transplantation. J. Clin. Invest. 112, 1095-1107.
4. Andorsky, D.J., and Timmerman, J.M. (2008). Interleukin-21: Biology and application to cancer therapy. Expert Opin. Biol. Ther. 8, 1295-1307.
5. Berger, C., Jensen, M.C., Lansdorp, P.M., Gough, M., Elliott, C., and Riddell, S.R. (2008). Adoptive transfer of effector CD8+ T cells derived from central memory cells establishes persistent T cell memory in primates. J. Clin. Invest. 118, 294-305.
6. Berger, C., Berger, M., Hackman, R.C., Gough, M., Elliott, C., Jensen, M.C., and Riddell, S.R. (2009). Safety and im-munological effects of IL-15 administration in nonhuman primates. Blood 2009 Jul 15 [Epub ahead of print].
7. Boesteanu, A.C., and Katsikis, P.D. (2009). Memory T cells need CD28 costimulation to remember. Semin. Immunol. 21, 69-77.
8. Bollard, C.M., Rossig, C., Calonge, M.J., Huls, M.H., Wagner, H.J., Massague, J., Brenner, M.K., Heslop, H.E., and Rooney, C.M. (2002). Adapting a transforming growth factor b-related tumor protection strategy to enhance antitumor immunity. Blood 99, 3179-3187.
9. Bollard, C.M., Aguilar, L., Straathof, K.C., Gahn, B., Huls, M.H., Rousseau, A., Sixbey, J., Gresik, M.V., Carrum, G., Hudson, M., Dilloo, D., Gee, A., Brenner, M.K., Rooney, C.M., and Heslop, H.E. (2004). Cytotoxic T lymphocyte therapy for Epstein-Barr virus+ Hodgkin's disease. J. Exp. Med. 200, 1623-1633.
10. Bonini, C., Ferrari, G., Verzeletti, S., Servida, P., Zappone, E., Ruggieri, L., Ponzoni, M., Rossini, S., Mavilio, F., Traversari, C., and Bordignon, C. (1997). HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia. Science 276, 1719-1724.
11. Bonini, C., Grez, M., Traversari, C., Ciceri, F., Marktel, S., Ferrari, G., Dinauer, M., Sadat, M., Aiuti, A., Deola, S., Radrizzani, M., Hagenbeek, A., Apperley, J., Ebeling, S., Martens, A., Kolb, H.J., Weber, M., Lotti, F., Grande, A., Weissinger, E., Bueren, J.A., Lamana, M., Falkenburg, J.H., Heemskerk, M.H., Austin, T., Kornblau, S., Marini, F., Benati, C., Magnani, Z., Cazzani-ga, S., Toma, S., Gallo-Stampino, C., Introna, M., Slavin, S., Greenberg, P.D., Bregni, M., Mavilio, F., and Bordignon, C. (2003). Safety of retroviral gene marking with a truncated NGF receptor. Nat. Med. 9, 367-369.
12. Bordignon, C., Notarangelo, L.D., Nobili, N., Ferrari, G., Casorati, G., Panina, P., Mazzolari, E., Maggioni, D., Rossi, C., Servida, P., Ugazio, A.G., and Mavilio, F. (1995). Gene therapy in peripheral blood lymphocytes and bone marrow for ADA-immunodeficient patients. Science 270, 470-475.
13. Brenner, M.K., and Heslop, H.E. (2003). Is retroviral gene marking too dangerous to use? Cytotherapy 5, 190-193.
14. Brentjens, R., Riviere, I., Hollyman, D., Taylor, C., Nikhamin, Y., Stefanski, J., Lee, J., Yeh, R., Santos, E., and Sadelain, M. (2009). Unexpected toxicity of cyclophosphamide followed by adoptively transferred CD19-targeted T cells in a patient with bulky CLL [abstract]. Mol. Ther. 17(Suppl. 1), 2009.
15. Cavalieri, S., Cazzaniga, S., Geuna, M., Magnani, Z., Bordignon, C., Naldini, L., and Bonini, C. (2003). Human T lymphocytes transduced by lentiviral vectors in the absence of TCR activation maintain an intact immune competence. Blood 102, 497-505.
16. Comoli, P., Pedrazzoli, P., Maccario, R., Basso, S., Carminati, O., Labirio, M., Schiavo, R., Secondino, S., Frasson, C., Perotti, C., Moroni, M., Locatelli, F., and Siena, S. (2005). Cell therapy of stage IV nasopharyngeal carcinoma with autologous Epstein-Barr virus-targeted cytotoxic T lymphocytes. J. Clin. Oncol. 23, 8942-8949.
17. Cooper, L.J., Topp, M.S., Serrano, L.M., Gonzalez, S., Chang, W.C., Naranjo, A., Wright, C., Popplewell, L., Raubitschek, A., Forman, S.J., and Jensen, M.C. (2003). T-cell clones can be rendered specific for CD19: Toward the selective augmentation of the graft-versus-B-lineage leukemia effect. Blood 101, 1637-1644.
18. Cooper, M.A., Fehniger, T.A., Turner, S.C., Chen, K.S., Ghaheri, B.A., Ghayur, T., Carson, W.E., and Caligiuri, M.A. (2001). Human natural killer cells: A unique innate immuno-regulatory role for the CD56 bright subset. Blood 97, 3146-3151.
19. Dieli, F., Vermijlen, D., Fulfaro, F., Caccamo, N., Meraviglia, S., Cicero, G., Roberts, A., Buccheri, S., D'Asaro, M., Gebbia, N., Salerno, A., Eberl, M., and Hayday, A.C. (2007). Targeting human gd T cells with zoledronate and interleukin-2 for im-munotherapy of hormone-refractory prostate cancer. Cancer Res. 67, 7450-7457.
20. Di Stasi, A., De Angelis, B., Rooney, C.M., Zhang, L., Mahen-dravada, A., Foster, A.E., Heslop, H.E., Brenner, M.K., Dotti, G., and Savoldo, B. (2009). T lymphocytes coexpressing CCR4 and a chimeric antigen receptor targeting CD30 have improved homing and antitumor activity in a Hodgkin tumor model. Blood 113, 6392-6402.
21. Dotti, G., Savoldo, B., Pule, M., Straathof, K.C., Biagi, E., Yvon, E., Vigouroux, S., Brenner, M.K., and Rooney, C.M. (2005). Human cytotoxic T lymphocytes with reduced sensitivity to Fas-induced apoptosis. Blood 105, 4677-4684.
22. Dudley, M.E., and Rosenberg, S.A. (2003). Adoptive-cell-transfer therapy for the treatment of patients with cancer. Nat. Rev. Cancer 3, 666-675.
23. Dudley, M.E., Wunderlich, J.R., Yang, J.C., Sherry, R.M., Topa-lian, S.L., Restifo, N.P., Royal, R.E., Kammula, U., White, D.E., Mavroukakis, S.A., Rogers, L.J., Gracia, G.J., Jones, S.A., Mangiameli, D.P., Pelletier, M.M., Gea-Banacloche, J., Robinson, M.R., Berman, D.M., Filie, A.C., Abati, A., and Rosenberg, S.A. (2005). Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J. Clin. Oncol. 23, 2346-2357.
24. Dudley, M.E., Yang, J.C., Sherry, R., Hughes, M.S., Royal, R., Kammula, U., Robbins, P.F., Huang, J., Citrin, D.E., Leitman, S.F., Wunderlich, J., Restifo, N.P., Thomasian, A., Downey, S.G., Smith, F.O., Klapper, J., Morton, K., Laurencot, C., White, D.E., and Rosenberg, S.A. (2008). Adoptive cell therapy for patients with metastatic melanoma: Evaluation of intensive myeloablative chemoradiation preparative regimens. J. Clin. Oncol. 26, 5233-5239.
25. Duraiswamy, J., Burrows, J.M., Bharadwaj, M., Burrows, S.R., Cooper, L., Pimtanothai, N., and Khanna, R. (2003). Ex vivo analysis of T-cell responses to Epstein-Barr virus-encoded oncogene latent membrane protein 1 reveals highly conserved epitope sequences in virus isolates from diverse geographic regions. J. Virol. 77, 7401-7410.
26. Eshhar, Z., Waks, T., Gross, G., and Schindler, D.G. (1993). Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the g or z subunits of the immunoglobulin and T-cell receptors. Proc. Natl. Acad. Sci. U.S.A. 90, 720-724.
27. Finney, H.M., Lawson, A.D., Bebbington, C.R., and Weir, A.N. (1998). Chimeric receptors providing both primary and co-stimulatory signaling in T cells from a single gene product. J. Immunol. 161, 2791-2797.
28. Gattinoni, L., Finkelstein, S.E., Klebanoff, C.A., Antony, P.A., Palmer, D.C., Spiess, P.J., Hwang, L.N., Yu, Z., Wrzesinski, C., Heimann, D.M., Surh, C.D., Rosenberg, S.A., and Restifo, N.P. (2005). Removal of homeostatic cytokine sinks by lymphode-pletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells. J. Exp. Med. 202, 907-912.
29. Hacein-Bey-Abina, S., Von Kalle, C., Schmidt, M., Le Deist, F., Wulffraat, N., McIntyre, E., Radford, I., Villeval, J.L., Fraser, C.C., Cavazzana-Calvo, M., and Fischer, A. (2003). A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. N. Engl. J. Med. 348, 255-256.
30. Hacein-Bey-Abina, S., Garrigue, A., Wang, G.P., Soulier, J., Lim, A., Morillon, E., Clappier, E., Caccavelli, L., Delabesse, E., Beldjord, K., Asnafi, V., Macintyre, E., Dal, C.L., Radford, I., Brousse, N., Sigaux, F., Moshous, D., Hauer, J., Borkhardt, A., Belohradsky, B.H., Wintergerst, U., Velez, M.C., Leiva, L., Sorensen, R., Wulffraat, N., Blanche, S., Bushman, F.D., Fischer, A., and Cavazzana-Calvo, M. (2008). Insertional on-cogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. J. Clin. Invest. 118, 3132-3142.
31. Heslop, H.E., Ng, C.Y., Li, C., Smith, C.A., Loftin, S.K., Krance, R.A., Brenner, M.K., and Rooney, C.M. (1996). Long-term restoration of immunity against Epstein-Barr virus infection by adoptive transfer of gene-modified virus-specific T lymphocytes. Nat. Med. 2, 551-555.
32. Hombach, A., Heuser, C., Sircar, R., Tillmann, T., Diehl, V., Pohl, C., and Abken, H. (1999). Characterization of a chimeric T-cell receptor with specificity for the Hodgkin's lymphoma-associated CD30 antigen. J. Immunother. 22, 473-480.
33. Hu, W.S., and Pathak, V.K. (2000). Design of retroviral vectors and helper cells for gene therapy. Pharmacol. Rev. 52, 493-511.
34. Huang, X., Guo, H., Kang, J., Choi, S., Zhou, T.C., Tammana, S., Lees, C.J., Li, Z.Z., Milone, M., Levine, B.L., Tolar, J., June, C.H., Scott, M.R., Wagner, J.E., Blazar, B.R., and Zhou, X. (2008). Sleeping Beauty transposon-mediated engineering of human primary T cells for therapy of CD19+ lymphoid malignancies. Mol. Ther. 16, 580-589.
35. Imai, C., Mihara, K., Andreansky, M., Nicholson, I.C., Pui, C.H., Geiger, T.L., and Campana, D. (2004). Chimeric receptors with 4-1BB signaling capacity provoke potent cytotoxicity against acute lymphoblastic leukemia. Leukemia 18, 676-684.
36. Imai, C., Iwamoto, S., and Campana, D. (2005). Genetic modification of primary natural killer cells overcomes inhibitory signals and induces specific killing of leukemic cells. Blood 106, 376-383.
37. Jensen, M.C., Cooper, L.J., Wu, A.M., Forman, S.J., and Rau-bitschek, A. (2003). Engineered CD20-specific primary human cytotoxic T lymphocytes for targeting B-cell malignancy. Cy-totherapy 5, 131-138.
38. Kaech, S.M., Tan, J.T., Wherry, E.J., Konieczny, B.T., Surh, C.D., and Ahmed, R. (2003). Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells. Nat. Immunol. 4, 1191-1198.
39. Kershaw, M.H., Wang, G., Westwood, J.A., Pachynski, R.K., Tiffany, H.L., Marincola, F.M., Wang, E., Young, H.A., Murphy, P.M., and Hwu, P. (2002). Redirecting migration of T cells to chemokine secreted from tumors by genetic modification with CXCR2. Hum. Gene Ther. 13, 1971-1980.
40. Kershaw, M.H., Westwood, J.A., Parker, L.L., Wang, G., Eshhar, Z., Mavroukakis, S.A., White, D.E., Wunderlich, J.R., Cane-vari, S., Rogers-Freezer, L., Chen, C.C., Yang, J.C., Rosenberg, S.A., and Hwu, P. (2006). A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer. Clin. Cancer Res. 12, 6106-6115.
41. Kim, H., Peng, G., Hicks, J.M., Weiss, H.L., Van Meir, E.G., Brenner, M.K., and Yotnda, P. (2008). Engineering human tumor-specific cytotoxic T cells to function in a hypoxic environment. Mol. Ther. 16, 599-606.
42. Kowolik, C.M., Topp, M.S., Gonzalez, S., Pfeiffer, T., Olivares, S., Gonzalez, N., Smith, D.D., Forman, S.J., Jensen, M.C., and Cooper, L.J. (2006). CD28 costimulation provided through a CD19-specific chimeric antigen receptor enhances in vivo persistence and antitumor efficacy of adoptively transferred T cells. Cancer Res. 66, 10995-11004.
43. Lamers, C.H., Sleijfer, S., Vulto, A.G., Kruit, W.H., Kliffen, M., Debets, R., Gratama, J.W., Stoter, G., and Oosterwijk, E. (2006). Treatment of metastatic renal cell carcinoma with autologous T-lymphocytes genetically retargeted against carbonic anhy-drase IX: First clinical experience. J. Clin. Oncol. 24, e20-e22.
44. Landmeier, S., Altvater, B., Pscherer, S., Eing, B.R., Kuehn, J., Rooney, C.M., Juergens, H., and Rossig, C. (2007). Gene-engineered varicella-zoster virus reactive CD4+ cytotoxic T cells exert tumor-specific effector function. Cancer Res. 67, 8335-8343.
45. Liu, K., and Rosenberg, S.A. (2001). Transduction of an IL-2 gene into human melanoma-reactive lymphocytes results in their continued growth in the absence of exogenous IL-2 and maintenance of specific antitumor activity. J. Immunol. 167, 6356-6365.
46. Loskog, A., Giandomenico, V., Rossig, C., Pule, M., Dotti, G., and Brenner, M.K. (2006). Addition of the CD28 signaling domain to chimeric T-cell receptors enhances chimeric T-cell resistance to T regulatory cells. Leukemia 20, 1819-1828.
47. Ma, A., Koka, R., and Burkett, P. (2006). Diverse functions of IL-2, IL-15, and IL-7 in lymphoid homeostasis. Annu. Rev. Immunol. 24, 657-679.
48. Maher, J., Brentjens, R.J., Gunset, G., Riviere, I., and Sadelain, M. (2002). Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRz=CD28 receptor. Nat. Bio-technol. 20, 70-75.
49. Miller, D.G., Adam, M.A., and Miller, A.D. (1990). Gene transfer by retrovirus vectors occurs only in cells that are actively replicating at the time of infection. Mol. Cell. Biol. 10, 4239-4242.
50. Milone, M.C., Fish, J.D., Carpenito, C., Carroll, R.G., Binder, G.K., Teachey, D., Samanta, M., Lakhal, M., Gloss, B., net-Desnoyers, G., Campana, D., Riley, J.L., Grupp, S.A., and June, C.H. (2009). Chimeric receptors containing CD137 signal transduction domains mediate enhanced survival of T cells and increased antileukemic efficacy in vivo. Mol. Ther. 17, 1453-1464.
51. Mitchell, D.A., Karikari, I., Cui, X., Xie, W., Schmittling, R., and Sampson, J.H. (2008). Selective modification of antigen-specific T cells by RNA electroporation. Hum. Gene Ther. 19, 511-521.
52. Mitsuyasu, R.T., Anton, P.A., Deeks, S.G., Scadden, D.T., Con-nick, E., Downs, M.T., Bakker, A., Roberts, M.R., June, C.H., Jalali, S., Lin, A.A., Pennathur-Das, R., and Hege, K.M. (2000). Prolonged survival and tissue trafficking following adoptive transfer of CD4z gene-modified autologous CD4+ and CD8+ T cells in human immunodeficiency virus-infected subjects. Blood 96, 785-793.
53. Montini, E., Cesana, D., Schmidt, M., Sanvito, F., Ponzoni, M., Bartholomae, C., Sergi, S.L., Benedicenti, F., Ambrosi, A., Di Serio, C., Doglioni, C., Von Kalle, C., and Naldini, L. (2006). Hematopoietic stem cell gene transfer in a tumor-prone mouse model uncovers low genotoxicity of lentiviral vector integration. Nat. Biotechnol. 24, 687-696.
54. Morgan, R.A., Dudley, M.E., Wunderlich, J.R., Hughes, M.S., Yang, J.C., Sherry, R.M., Royal, R.E., Topalian, S.L., Kammula, U.S., Restifo, N.P., Zheng, Z., Nahvi, A., de Vries, C.R., Rogers-Freezer, L.J., Mavroukakis, S.A., and Rosenberg, S.A. (2006). Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 314, 126-129.
55. Naldini, L., Blomer, U., Gallay, P., Ory, D., Mulligan, R., Gage, F.H., Verma, I.M., and Trono, D. (1996). In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 272, 263-267.
56. Nanjappa, S.G., Walent, J.H., Morre, M., and Suresh, M. (2008). Effects of IL-7 on memory CD8 T cell homeostasis are influenced by the timing of therapy in mice. J. Clin. Invest. 118, 1027-1039.
57. Nanno, M., Shiohara, T., Yamamoto, H., Kawakami, K., and Ishikawa, H. (2007). gd T cells: Firefighters or fire boosters in the front lines of inflammatory responses. Immunol. Rev. 215, 103-113.
58. Park, J.R., Digiusto, D.L., Slovak, M., Wright, C., Naranjo, A., Wagner, J., Meechoovet, H.B., Bautista, C., Chang, W.C., Ostberg, J.R., and Jensen, M.C. (2007). Adoptive transfer of chimeric antigen receptor re-directed cytolytic T lymphocyte clones in patients with neuroblastoma. Mol. Ther. 15, 825-833.
59. Paulos, C.M., Suhoski, M.M., Plesa, G., Jiang, T., Basu, S., Golovina, T.N., Jiang, S., Aqui, N.A., Powell, D.J., Jr., Levine, B.L., Carroll, R.G., Riley, J.L., and June, C.H. (2008). Adoptive immunotherapy: Good habits instilled at youth have long-term benefits. Immunol. Res. 42, 182-196.
60. Poppema, S., Potters, M., Visser, L., and van den Berg, A.M. (1998). Immune escape mechanisms in Hodgkin's disease. Ann. Oncol. 9(Suppl. 5), S21-S24.
61. Powell, D.J., Jr., Dudley, M.E., Robbins, P.F., and Rosenberg, S.A. (2005). Transition of late-stage effector T cells to CD27+ CD28+ tumor-reactive effector memory T cells in humans after adoptive cell transfer therapy. Blood 105, 241-250.
62. Pule, M.A., Straathof, K.C., Dotti, G., Heslop, H.E., Rooney, C.M., and Brenner, M.K. (2005). A chimeric T cell antigen receptor that augments cytokine release and supports clonal expansion of primary human T cells. Mol. Ther. 12, 933-941.
63. Pule, M.A., Savoldo, B., Myers, G.D., Rossig, C., Russell, H.V., Dotti, G., Huls, M.H., Liu, E., Gee, A.P., Mei, Z., Yvon, E., Weiss, H.L., Liu, H., Rooney, C.M., Heslop, H.E., and Brenner, M.K. (2008). Virus-specific T cells engineered to coex-press tumor-specific receptors: Persistence and antitumor activity in individuals with neuroblastoma. Nat. Med. 14, 1264-1270.
64. Quintarelli, C., Vera, J.F., Savoldo, B., Giordano Attianese, G.M., Pule, M., Foster, A.E., Heslop, H.E., Rooney, C.M., Brenner, M.K., and Dotti, G. (2007). Co-expression of cytokine and suicide genes to enhance the activity and safety of tumor-specific cytotoxic T lymphocytes. Blood 110, 2793-2802.
65. Rischer, M., Pscherer, S., Duwe, S., Vormoor, J., Jurgens, H., and Rossig, C. (2004). Human gd T cells as mediators of chimaeric-receptor redirected anti-tumour immunity. Br. J. Haematol. 126, 583-592.
66. Robbins, P.F., Dudley, M.E., Wunderlich, J., El-Gamil, M., Li, Y.F., Zhou, J., Huang, J., Powell, D.J., Jr., and Rosenberg, S.A. (2004). Cutting edge: Persistence of transferred lymphocyte clonotypes correlates with cancer regression in patients receiving cell transfer therapy. J. Immunol. 173, 7125-7130.
67. Rooney, C.M., Smith, C.A., Ng, C.Y., Loftin, S., Li, C., Krance, R.A., Brenner, M.K., and Heslop, H.E. (1995). Use of gene-modified virus-specific T lymphocytes to control Epstein-Barr-virus-related lymphoproliferation. Lancet 345, 9-13.
68. Rooney, C.M., Smith, C.A., Ng, C.Y., Loftin, S.K., Sixbey, J.W., Gan, Y., Srivastava, D.K., Bowman, L.C., Krance, R.A., Brenner, M.K., and Heslop, H.E. (1998). Infusion of cytotoxic T cells for the prevention and treatment of Epstein-Barr virus-induced lymphoma in allogeneic transplant recipients. Blood 92, 1549-1555.
69. Rosenberg, S.A., Aebersold, P., Cornetta, K., Kasid, A., Morgan, R.A., Moen, R., Karson, E.M., Lotze, M.T., Yang, J.C., Topa-lian, S.L., Merino, M.J., Culver, K., Miller, A.D., Blaese, R.M., and Anderson, W.F. (1990). Gene transfer into humans- immunotherapy of patients with advanced melanoma, using tumor-infiltrating lymphocytes modified by retroviral gene transduction. N. Engl. J. Med. 323, 570-578.
70. Rosenberg, S.A., Yannelli, J.R., Yang, J.C., Topalian, S.L., Schwartzentruber, D.J., Weber, J.S., Parkinson, D.R., Seipp, C.A., Einhorn, J.H., and White, D.E. (1994). Treatment of patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and interleukin 2. J. Natl. Cancer Inst. 86, 1159-1166.
71. Rosenberg, S.A., Sportes, C., Ahmadzadeh, M., Fry, T.J., Ngo, L.T., Schwarz, S.L., Stetler-Stevenson, M., Morton, K.E., Mavroukakis, S.A., Morre, M., Buffet, R., Mackall, C.L., and Gress, R.E. (2006). IL-7 administration to humans leads to expansion of CD8+ and CD4+ cells but a relative decrease of CD4+ T-regulatory cells. J. Immunother. 29, 313-319.
72. Rosenberg, S.A., Restifo, N.P., Yang, J.C., Morgan, R.A., and Dudley, M.E. (2008). Adoptive cell transfer: A clinical path to effective cancer immunotherapy. Nat. Rev. Cancer 8, 299-308.
73. Rossig, C., Bollard, C.M., Nuchtern, J.G., Merchant, D.A., and Brenner, M.K. (2001). Targeting of GD2-positive tumor cells by human T lymphocytes engineered to express chimeric T-cell receptor genes. Int. J. Cancer 94, 228-236.
74. Rossig, C., Bollard, C.M., Nuchtern, J.G., Rooney CM and Brenner MK (2002). Epstein-Barr virus-specific human T lymphocytes expressing antitumor chimeric T-cell receptors: potential for improved immunotherapy. Blood 99 2009-2016.
75. Ruggeri, L., Mancusi, A., Burchielli, E., Capanni, M., Carotti, A., Aloisi, T., Aversa, F., Martelli, M.F., and Velardi, A. (2008). NK cell alloreactivity and allogeneic hematopoietic stem cell transplantation. Blood Cells Mol. Dis. 40, 84-90.
76. Sadelain, M., Brentjens, R., and Riviere, I. (2009). The promise and potential pitfalls of chimeric antigen receptors. Curr. Opin. Immunol. 21, 215-223.
77. Savoldo, B., Rooney, C.M., Di Stasi, A., Abken, H., Hombach, A., Foster, A.E., Zhang, L., Heslop, H.E., Brenner, M.K., and Dotti, G. (2007). Epstein-Barr virus specific cytotoxic T lymphocytes expressing the anti-CD30z artificial chimeric T-cell receptor for immunotherapy of Hodgkin disease. Blood 110, 2620-2630.
78. Schluns, K.S., Kieper, W.C., Jameson, S.C., and Lefrancois, L. (2000). Interleukin-7 mediates the homeostasis of naive and memory CD8 T cells in vivo. Nat. Immunol. 1, 426-432.
79. Singh, H., Manuri, P.R., Olivares, S., Dara, N., Dawson, M.J., Huls, H., Hackett, P.B., Kohn, D.B., Shpall, E.J., Champlin, R.E., and Cooper, L.J. (2008). Redirecting specificity of T-cell populations for CD19 using the Sleeping Beauty system. Cancer Res. 68, 2961-2971.
80. Sportes, C., Hakim, F.T., Memon, S.A., Zhang, H., Chua, K.S., Brown, M.R., Fleisher, T.A., Krumlauf, M.C., Babb, R.R., Chow, C.K., Fry, T.J., Engels, J., Buffet, R., Morre, M., Amato, R.J., Venzon, D.J., Korngold, R., Pecora, A., Gress, R.E., and Mackall, C.L. (2008). Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets. J. Exp. Med. 205, 1701-1714.
81. Stastny, M.J., Brown, C.E., Ruel, C., and Jensen, M.C. (2007). Medulloblastomas expressing IL13Ra2 are targets for IL13-zetakine+ cytolytic T cells. J. Pediatr. Hematol. Oncol. 29, 669-677.
82. Straathof, K.C., Bollard, C.M., Popat, U., Huls, M.H., Lopez, T., Morriss, M.C., Gresik, M.V., Gee, A.P., Russell, H.V., Brenner, M.K., Rooney, C.M., and Heslop, H.E. (2005a). Treatment of nasopharyngeal carcinoma with Epstein-Barr virus-specific T lymphocytes. Blood 105, 1898-1904.
83. Straathof, K.C., Pule, M.A., Yotnda, P., Dotti, G., Vanin, E.F., Brenner, M.K., Heslop, H.E., Spencer, D.M., and Rooney, C.M. (2005b). An inducible caspase 9 safety switch for T-cell therapy. Blood 105, 4247-4254.
84. Till, B.G., Jensen, M.C., Wang, J., Chen, E.Y., Wood, B.L., Greisman, H.A., Qian, X., James, S.E., Raubitschek, A., For-man, S.J., Gopal, A.K., Pagel, J.M., Lindgren, C.G., Greenberg, P.D., Riddell, S.R., and Press, O.W. (2008). Adoptive im-munotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells. Blood 112, 2261-2271.
85. Vera, J., Savoldo, B., Vigouroux, S., Biagi, E., Pule, M., Rossig, C., Wu, J., Heslop, H.E., Rooney, C.M., Brenner, M.K., and Dotti, G. (2006). T lymphocytes redirected against the k light chain of human immunoglobulin efficiently kill mature B lymphocyte-derived malignant cells. Blood 108, 3890-3897.
86. Vera, J.F., Hoyos, V., Savoldo, B., Quintarelli, C., Giordano At-tianese, G.M., Leen, A.M., Liu, H., Foster, A.E., Heslop, H.E., Rooney, C.M., Brenner, M.K., and Dotti, G. (2009). Genetic manipulation of tumor-specific cytotoxic T lymphocytes to restore responsiveness to IL-7. Mol. Ther. 17, 880-888.
87. C.C., Leitman, S.F., Palensky, J., Wittes, J., Davey, R.T., Jr., Falloon, J., Polis, M.A., Kovacs, J.A., Broad, D.F., Levine, B.L., Roberts, M.R., Masur, H., and Lane, H.C. (2000). Long-term in vivo survival of receptor-modified syngeneic T cells in patients with human immunodeficiency virus infection. Blood 96, 467-474.
88. Wilson, M.H., Coates, C.J., and George, A.L., Jr. (2007). PiggyBac transposon-mediated gene transfer in human cells. Mol. Ther. 15, 139-145.
89. Yee, C., Thompson, J.A., Byrd, D., Riddell, S.R., Roche, P., Celis, E., and Greenberg, P.D. (2002). Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastatic melanoma: In vivo persistence, migration, and antitumor effect of transferred T cells. Proc. Natl. Acad. Sci. U.S.A. 99, 16168-16173.
90. Zou, W. (2005). Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat. Rev. Cancer 5, 263-274