Adoptive T-cell therapy for cancer: The era of engineered T cells

European Journal of Immunology

Volumn 45, Issue 9, 2015, Pages 2457-2469

  Bonini, Chiara ^a   Mondino, Anna ^a  

^a SAN RAFFAELE HOSPITAL   (Italy)

Author keywords

Adoptive T cell therapy; Chimeric antigen receptor; Genetic engineering; Immunotherapy; T cells; T cell receptor

Indexed keywords

CHIMERIC ANTIGEN RECEPTOR; IMMUNOSUPPRESSIVE AGENT; INTERLEUKIN 15; T LYMPHOCYTE RECEPTOR; TOCILIZUMAB; CHIMERIC PROTEIN; LYMPHOCYTE ANTIGEN RECEPTOR; TUMOR ANTIGEN;

ADOPTIVE IMMUNOTHERAPY; CANCER IMMUNOTHERAPY; CELL FUNCTION; CELL THERAPY; CYTOKINE RELEASE SYNDROME; GENETIC ENGINEERING; GRAFT VERSUS HOST REACTION; HUMAN; IMMUNOLOGICAL TOLERANCE; KIDNEY CARCINOMA; METASTATIC MELANOMA; NONHUMAN; PRIORITY JOURNAL; REVIEW; SUICIDE GENE THERAPY; T CELL THERAPY; TRANSFORMED CELL; TUMOR IMMUNITY; BIOLOGICAL THERAPY; CELL ENGINEERING; FORECASTING; GENE EXPRESSION; GENE THERAPY; GENETICS; IMMUNOLOGY; METABOLISM; NEOPLASMS; PATHOLOGY; PROCEDURES; SUICIDE TRANSGENE; T LYMPHOCYTE; TRANSPLANTATION; TRENDS;

ANTIGENS, NEOPLASM; CELL ENGINEERING; CELL- AND TISSUE-BASED THERAPY; FORECASTING; GENE EXPRESSION; GENES, TRANSGENIC, SUICIDE; GENETIC THERAPY; HUMANS; IMMUNOTHERAPY, ADOPTIVE; MUTANT CHIMERIC PROTEINS; NEOPLASMS; RECEPTORS, ANTIGEN, T-CELL; T-LYMPHOCYTES;

EID: 84940956131     PISSN: 00142980     EISSN: 15214141     Source Type: Journal    
DOI: 10.1002/eji.201545552     Document Type: Review

References (133)

1. Hinrichs, C. S. and Rosenberg, S. A., Exploiting the curative potential of adoptive T-cell therapy for cancer. Immunol. Rev. 2014. 257: 56-71.
2. Patriarca, F., Luznik, L., Medeot, M., Zecca, M., Bacigalupo, A., Di Bartolomeo, P., Arcese, W. et al., Experts' considerations on HLA-haploidentical stem cell transplantation. Eur. J. Haematol. 2014. 93: 187-197.
3. Storb, R., Gyurkocza, B., Storer, B. E., Sorror, M. L., Blume, K., Niederwieser, D., Chauncey, T. R. et al., Graft-versus-host disease and graft-versus-tumor effects after allogeneic hematopoietic cell transplantation. J. Clin. Oncol. 2013. 31: 1530-1538.
4. Vago, L., Oliveira, G., Bondanza, A., Noviello, M., Soldati, C., Ghio, D., Brigida, I. et al., T-cell suicide gene therapy prompts thymic renewal in adults after hematopoietic stem cell transplantation. Blood 2012. 120: 1820-1830.
5. Crucitti, L., Crocchiolo, R., Toffalori, C., Mazzi, B., Greco, R., Signori, A., Sizzano, F. et al., Incidence, risk factors and clinical outcome of leukemia relapses with loss of the mismatched HLA after partially incompatible hematopoietic stem cell transplantation. Leukemia 2014.
6. Demirer, T., Barkholt, L., Blaise, D., Pedrazzoli, P., Aglietta, M., Carella, A. M., Bay, J. O. et al., Transplantation of allogeneic hematopoietic stem cells: an emerging treatment modality for solid tumors. Nat. Clin. Pract. Oncol. 2008. 5: 256-267.
7. Passweg, J. R., Baldomero, H., Bader, P., Bonini, C., Cesaro, S., Dreger, P., Duarte, R. F. et al., Hematopoietic SCT in Europe 2013: recent trends in the use of alternative donors showing more haploidentical donors but fewer cord blood transplants. Bone Marrow Transplant. 2015. 50: 476-482.
8. Filatenkov, A., Muller, A. M., Tseng, W. W., Dejbakhsh-Jones, S., Winer, D., Luong, R., Shizuru, J. A. et al., Ineffective vaccination against solid tumors can be enhanced by hematopoietic cell transplantation. J. Immunol. 2009. 183: 7196-7203.
9. Rezvani, K., Posttransplantation vaccination: concepts today and on the horizon. Hematology Am. Soc. Hematol. Educ. Program 2011. 2011: 299-304.
10. Hess Michelini, R., Freschi, M., Manzo, T., Jachetti, E., Degl'innocenti, E., Grioni, M., Basso, V. et al., Concomitant tumor and minor histocompatibility antigen-specific immunity initiate rejection and maintain remission from established spontaneous solid tumors. Cancer Res 2010. 70: 3505-3514.
11. Hess Michelini, R., Manzo, T., Sturmheit, T., Basso, V., Rocchi, M., Freschi, M., Listopad, J. et al., Vaccine-instructed intratumoral IFN-gamma enables regression of autochthonous mouse prostate cancer in allogeneic T-cell transplantation. Cancer Res. 2013. 73: 4641-4652.
12. Dudley, M. E., Wunderlich, J. R., Yang, J. C., Sherry, R. M., Topalian, S. L., Restifo, N. P., Royal, R. E. et al., Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J. Clin. Oncol. 2005. 23: 2346-2357.
13. Rosenberg, S. A. and Restifo, N. P., Adoptive cell transfer as personalized immunotherapy for human cancer. Science 2015. 348: 62-68.
14. Rosenberg, S. A., Cell transfer immunotherapy for metastatic solid cancer-what clinicians need to know. Nat. Rev. Clin. Oncol. 2011. 8: 577-585.
15. Baldan, V., Griffiths, R., Hawkins, R. E. and Gilham, D. E., Efficient and reproducible generation of tumour-infiltrating lymphocytes for renal cell carcinoma. Br. J. Cancer 2015. 112: 1510-1518.
16. Hwang, W. T., Adams, S. F., Tahirovic, E., Hagemann, I. S. and Coukos, G., Prognostic significance of tumor-infiltrating T cells in ovarian cancer: a meta-analysis. Gynecol. Oncol. 2012. 124: 192-198.
17. Reissfelder, C., Stamova, S., Gossmann, C., Braun, M., Bonertz, A., Walliczek, U., Grimm, M. et al., Tumor-specific cytotoxic T lymphocyte activity determines colorectal cancer patient prognosis. J. Clin. Investig. 2015. 125: 739-751.
18. Salgado, R., Denkert, C., Demaria, S., Sirtaine, N., Klauschen, F., Pruneri, G., Wienert, S. et al., The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann. Oncol. 2015. 26: 259-271.
19. Svane, I. M. and Verdegaal, E. M., Achievements and challenges of adoptive T cell therapy with tumor-infiltrating or blood-derived lymphocytes for metastatic melanoma: what is needed to achieve standard of care? Cancer Immunol. Immunother. 2014. 63: 1081-1091.
20. Greco, R., Oliveira, G., Stanghellini, M. T., Vago, L., Bondanza, A., Peccatori, J., Cieri, N. et al., Improving the safety of cell therapy with the TK-suicide gene. Front. Pharmacol. 2015. 6: 95.
21. Parkhurst, M. R., Yang, J. C., Langan, R. C., Dudley, M. E., Nathan, D. A., Feldman, S. A., Davis, J. L. et al., T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis. Mol. Ther. 2011. 19: 620-626.
22. Chinnasamy, N., Wargo, J. A., Yu, Z., Rao, M., Frankel, T. L., Riley, J. P., Hong, J. J. et al., A TCR targeting the HLA-A*0201-restricted epitope of MAGE-A3 recognizes multiple epitopes of the MAGE-A antigen superfamily in several types of cancer. J. Immunol. 2011. 186: 685-696.
23. Grupp, S. A., Kalos, M., Barrett, D., Aplenc, R., Porter, D. L., Rheingold, S. R., Teachey, D. T. et al., Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N. Engl. J. Med. 2013. 368: 1509-1518.
24. Park, J. R., Digiusto, D. L., Slovak, M., Wright, C., Naranjo, A., Wagner, J., Meechoovet, H. B. et al., Adoptive transfer of chimeric antigen receptor re-directed cytolytic T lymphocyte clones in patients with neuroblastoma. Mol. Ther. 2007. 15: 825-833.
25. June, C. H., Maus, M. V., Plesa, G., Johnson, L. A., Zhao, Y., Levine, B. L., Grupp, S. A. et al., Engineered T cells for cancer therapy. Cancer Immunol. Immunother. 2014. 63: 969-975.
26. Dotti, G., Gottschalk, S., Savoldo, B. and Brenner, M. K., Design and development of therapies using chimeric antigen receptor-expressing T cells. Immunol. Rev. 2014. 257: 107-126.
27. Gschweng, E., De Oliveira, S. and Kohn, D. B., Hematopoietic stem cells for cancer immunotherapy. Immunol. Rev. 2014. 257: 237-249.
28. Cieri, N., Mastaglio, S., Oliveira, G., Casucci, M., Bondanza, A. and Bonini, C., Adoptive immunotherapy with genetically modified lymphocytes in allogeneic stem cell transplantation. Immunol. Rev. 2014. 257: 165-180.
29. Stromnes, I. M., Schmitt, T. M., Chapuis, A. G., Hingorani, S. R. and Greenberg, P. D., Re-adapting T cells for cancer therapy: from mouse models to clinical trials. Immunol. Rev. 2014. 257: 145-164.
30. Gill, S. and June, C. H., Going viral: chimeric antigen receptor T-cell therapy for hematological malignancies. Immunol. Rev. 2015. 263: 68-89.
31. Jensen, M. C. and Riddell, S. R., Designing chimeric antigen receptors to effectively and safely target tumors. Curr. Opin. Immunol. 2015. 33C: 9-15.
32. Curran, K. J. and Brentjens, R. J., Chimeric antigen receptor T cells for cancer immunotherapy. J. Clin. Oncol. 2015. 33: 1703-1706.
33. Duong, C. P., Yong, C. S., Kershaw, M. H., Slaney, C. Y. and Darcy, P. K., Cancer immunotherapy utilizing gene-modified T cells: from the bench to the clinic. Mol. Immunol. 2015.
34. Bonini, C., Ferrari, G., Verzeletti, S., Servida, P., Zappone, E., Ruggieri, L., Ponzoni, M. et al., HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia. Science 1997. 276: 1719-1724.
35. Horowitz, M. M., Gale, R. P., Sondel, P. M., Goldman, J. M., Kersey, J., Kolb, H. J., Rimm, A. A. et al., Graft-versus-leukemia reactions after bone marrow transplantation. Blood 1990. 75: 555-562.
36. Smee, D. F., Martin, J. C., Verheyden, J. P. and Matthews, T. R., Anti-herpesvirus activity of the acyclic nucleoside 9-(1, 3-dihydroxy-2-propoxymethyl)guanine. Antimicrob. Agents Chemother. 1983. 23: 676-682.
37. Oliveira, G., Greco, R., Lupo-Stanghellini, M. T., Vago, L. and Bonini, C., Use of TK-cells in haploidentical hematopoietic stem cell transplantation. Curr. Opin. Hematol. 2012. 19: 427-433.
38. Ciceri, F., Bonini, C., Stanghellini, M. T., Bondanza, A., Traversari, C., Salomoni, M., Turchetto, L. et al., Infusion of suicide-gene-engineered donor lymphocytes after family haploidentical haemopoietic stem-cell transplantation for leukaemia (the TK007 trial): a non-randomised phase I-II study. Lancet Oncol. 2009. 10: 489-500.
39. Ciceri, F., Labopin, M., Aversa, F., Rowe, J. M., Bunjes, D., Lewalle, P., Nagler, A. et al., A survey of fully haploidentical hematopoietic stem cell transplantation in adults with high-risk acute leukemia: a risk factor analysis of outcomes for patients in remission at transplantation. Blood 2008. 112: 3574-3581.
40. Jones, B. S., Lamb, L. S., Goldman, F. and Di Stasi, A., Improving the safety of cell therapy products by suicide gene transfer. Front Pharmacol. 2014. 5: 254.
41. Zhou, X., Di Stasi, A., Tey, S. K., Krance, R. A., Martinez, C., Leung, K. S., Durett, A. G. et al., Long-term outcome after haploidentical stem cell transplant and infusion of T cells expressing the inducible caspase 9 safety transgene. Blood 2014. 123: 3895-3905.
42. Zhou, X., Dotti, G., Krance, R. A., Martinez, C. A., Naik, S., Kamble, R. T., Durett, A. G. et al., Inducible caspase-9 suicide gene controls adverse effects from alloreplete T cells after haploidentical stem cell transplantation. Blood 2015. 125: 4103-4113.
43. Griffioen, M., van Egmond, E. H., Kester, M. G., Willemze, R., Falkenburg, J. H. and Heemskerk, M. H., Retroviral transfer of human CD20 as a suicide gene for adoptive T-cell therapy. Haematologica 2009. 94: 1316-1320.
44. Wang, X., Chang, W. C., Wong, C. W., Colcher, D., Sherman, M., Ostberg, J. R., Forman, S. J. et al., A transgene-encoded cell surface polypeptide for selection, in vivo tracking, and ablation of engineered cells. Blood 2011. 118: 1255-1263.
45. Berger, C., Flowers, M. E., Warren, E. H. and Riddell, S. R., Analysis of transgene-specific immune responses that limit the in vivo persistence of adoptively transferred HSV-TK-modified donor T cells after allogeneic hematopoietic cell transplantation. Blood 2006. 107: 2294-2302.
46. Traversari, C., Marktel, S., Magnani, Z., Mangia, P., Russo, V., Ciceri, F., Bonini, C. et al., The potential immunogenicity of the TK suicide gene does not prevent full clinical benefit associated with the use of TK-transduced donor lymphocytes in HSCT for hematologic malignancies. Blood 2007. 109: 4708-4715.
47. Blankenstein, T., Leisegang, M., Uckert, W. and Schreiber, H., Targeting cancer-specific mutations by T cell receptor gene therapy. Curr. Opin. Immunol. 2015. 33C: 112-119.
48. Cheever, M. A., Allison, J. P., Ferris, A. S., Finn, O. J., Hastings, B. M., Hecht, T. T., Mellman, I. et al., The prioritization of cancer antigens: a national cancer institute pilot project for the acceleration of translational research. Clin. Cancer Res. 2009. 15: 5323-5337.
49. Johnson, L. A., Morgan, R. A., Dudley, M. E., Cassard, L., Yang, J. C., Hughes, M. S., Kammula, U. S. et al., Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. Blood 2009. 114: 535-546.
50. Morgan, R. A., Chinnasamy, N., Abate-Daga, D., Gros, A., Robbins, P. F., Zheng, Z., Dudley, M. E. et al., Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy. J. Immunother. 2013. 36: 133-151.
51. Robbins, P. F., Kassim, S. H., Tran, T. L., Crystal, J. S., Morgan, R. A., Feldman, S. A., Yang, J. C. et al., A pilot trial using lymphocytes genetically engineered with an NY-ESO-1-reactive T-cell Receptor: long-term follow-up and correlates with response. Clin. Cancer Res. 2014. 21: 1019-1027.
52. Robbins, P. F., Morgan, R. A., Feldman, S. A., Yang, J. C., Sherry, R. M., Dudley, M. E., Wunderlich, J. R. et al., Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J. Clin. Oncol. 2011. 29: 917-924.
53. Vigneron, N., Stroobant, V., Van den Eynde, B. J. and van der Bruggen, P., Database of T cell-defined human tumor antigens: the 2013 update. Cancer Immun. 2013. 13: 15.
54. Tran, E., Turcotte, S., Gros, A., Robbins, P. F., Lu, Y. C., Dudley, M. E., Wunderlich, J. R. et al., Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science 2014. 344: 641-645.
55. Gubin, M. M., Zhang, X., Schuster, H., Caron, E., Ward, J. P., Noguchi, T., Ivanova, Y. et al., Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens. Nature 2014. 515: 577-581.
56. Kvistborg, P., Philips, D., Kelderman, S., Hageman, L., Ottensmeier, C., Joseph-Pietras, D., Welters, M. J. et al., Anti-CTLA-4 therapy broadens the melanoma-reactive CD8+ T cell response. Sci. Transl. Med. 2014. 6: 254ra128.
57. Rizvi, N. A., Hellmann, M. D., Snyder, A., Kvistborg, P., Makarov, V., Havel, J. J., Lee, W. et al., Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 2015. 348: 124-128.
58. Linnemann, C., Heemskerk, B., Kvistborg, P., Kluin, R. J., Bolotin, D. A., Chen, X., Bresser, K. et al., High-throughput identification of antigen-specific TCRs by TCR gene capture. Nat. Med. 2013. 19: 1534-1541.
59. Obenaus, M., Leitao, C., Leisegang, M., Chen, X., Gavvovidis, I., van der Bruggen, P., Uckert, W. et al., Identification of human T-cell receptors with optimal affinity to cancer antigens using antigen-negative humanized mice. Nat. Biotechnol. 2015. 33: 402-407.
60. Arber, C., Feng, X., Abhyankar, H., Romero, E., Wu, M. F., Heslop, H. E., Barth, P. et al., Survivin-specific T cell receptor targets tumor but not T cells. J. Clin. Invest. 2015. 125: 157-168.
61. Dossinger, G., Bunse, M., Bet, J., Albrecht, J., Paszkiewicz, P. J., Weissbrich, B., Schiedewitz, I. et al., MHC multimer-guided and cell culture-independent isolation of functional T cell receptors from single cells facilitates TCR identification for immunotherapy. PLoS One 2013. 8: e61384.
62. Linnemann, C., Mezzadra, R. and Schumacher, T. N., TCR repertoires of intratumoral T-cell subsets. Immunol. Rev. 2014. 257: 72-82.
63. Cameron, B. J., Gerry, A. B., Dukes, J., Harper, J. V., Kannan, V., Bianchi, F. C., Grand, F. et al., Identification of a Titin-derived HLA-A1-presented peptide as a cross-reactive target for engineered MAGE A3-directed T cells. Sci. Transl. Med. 2013. 5: 197ra103.
64. Linette, G. P., Stadtmauer, E. A., Maus, M. V., Rapoport, A. P., Levine, B. L., Emery, L., Litzky, L. et al., Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma. Blood 2013. 122: 863-871.
65. Schmitt, T. M., Aggen, D. H., Stromnes, I. M., Dossett, M. L., Richman, S. A., Kranz, D. M. and Greenberg, P. D., Enhanced-affinity murine T-cell receptors for tumor/self-antigens can be safe in gene therapy despite surpassing the threshold for thymic selection. Blood 2013. 122: 348-356.
66. Smith, F. O., Downey, S. G., Klapper, J. A., Yang, J. C., Sherry, R. M., Royal, R. E., Kammula, U. S. et al., Treatment of metastatic melanoma using interleukin-2 alone or in conjunction with vaccines. Clin. Cancer Res. 2008. 14: 5610-5618.
67. Bendle, G. M., Linnemann, C., Hooijkaas, A. I., Bies, L., de Witte, M. A., Jorritsma, A., Kaiser, A. D. et al., Lethal graft-versus-host disease in mouse models of T cell receptor gene therapy. Nat. Med. 2010. 16: 565-570.
68. van Loenen, M. M., de Boer, R., Amir, A. L., Hagedoorn, R. S., Volbeda, G. L., Willemze, R., van Rood, J. J. et al., Mixed T cell receptor dimers harbor potentially harmful neoreactivity. Proc. Natl. Acad. Sci. USA 2010. 107: 10972-10977.
69. Provasi, E., Genovese, P., Lombardo, A., Magnani, Z., Liu, P. Q., Reik, A., Chu, V. et al., Editing T cell specificity towards leukemia by zinc finger nucleases and lentiviral gene transfer. Nat. Med. 2012. 18: 807-815.
70. Bunse, M., Bendle, G. M., Linnemann, C., Bies, L., Schulz, S., Schumacher, T. N. and Uckert, W., RNAi-mediated TCR knockdown prevents autoimmunity in mice caused by mixed TCR dimers following TCR gene transfer. Mol. Ther. 2014. 22: 1983-1991.
71. Okamoto, S., Mineno, J., Ikeda, H., Fujiwara, H., Yasukawa, M., Shiku, H. and Kato, I., Improved expression and reactivity of transduced tumor-specific TCRs in human lymphocytes by specific silencing of endogenous TCR. Cancer Res. 2009. 69: 9003-9011.
72. Ochi, T., Fujiwara, H., Okamoto, S., An, J., Nagai, K., Shirakata, T., Mineno, J. et al., Novel adoptive T-cell immunotherapy using a WT1-specific TCR vector encoding silencers for endogenous TCRs shows marked antileukemia reactivity and safety. Blood 2011. 118: 1495-1503.
73. Porter, D. L., Levine, B. L., Kalos, M., Bagg, A. and June, C. H., Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N. Engl. J. Med. 2011. 365: 725-733.
74. Maude, S. L., Frey, N., Shaw, P. A., Aplenc, R., Barrett, D. M., Bunin, N. J., Chew, A. et al., Chimeric antigen receptor T cells for sustained remissions in leukemia. N. Engl. J. Med. 2014. 371: 1507-1517.
75. Maude, S. L., Barrett, D., Teachey, D. T. and Grupp, S. A., Managing cytokine release syndrome associated with novel T cell-engaging therapies. Cancer J. 2014. 20: 119-122.
76. Kenderian, S. S., Ruella, M., Shestova, O., Klichinsky, M., Aikawa, V., Morrissette, J. J., Scholler, J. et al., CD33 specific chimeric antigen receptor T cells exhibit potent preclinical activity against human acute myeloid leukemia. Leukemia 2015.
77. Maus, M. V., Grupp, S. A., Porter, D. L. and June, C. H., Antibody-modified T cells: CARs take the front seat for hematologic malignancies. Blood 2014. 123: 2625-2635.
78. Hudecek, M., Lupo-Stanghellini, M. T., Kosasih, P. L., Sommermeyer, D., Jensen, M. C., Rader, C. and Riddell, S. R., Receptor affinity and extracellular domain modifications affect tumor recognition by ROR1-specific chimeric antigen receptor T cells. Clin. Cancer Res. 2013. 19: 3153-3164.
79. Berger, C., Sommermeyer, D., Hudecek, M., Berger, M., Balakrishnan, A., Paszkiewicz, P. J., Kosasih, P. L. et al., Safety of targeting ROR1 in primates with chimeric antigen receptor-modified T cells. Cancer Immunol. Res. 2014. 3: 206-216.
80. Feldkamp, M. M., Lala, P., Lau, N., Roncari, L. and Guha, A., Expression of activated epidermal growth factor receptors, Ras-guanosine triphosphate, and mitogen-activated protein kinase in human glioblastoma multiforme specimens. Neurosurgery 1999. 45: 1442-1453.
81. Morgan, R. A., Johnson, L. A., Davis, J. L., Zheng, Z., Woolard, K. D., Reap, E. A., Feldman, S. A. et al., Recognition of glioma stem cells by genetically modified T cells targeting EGFRvIII and development of adoptive cell therapy for glioma. Hum. Gene Ther. 2012. 23: 1043-1053.
82. Johnson, L. A., Scholler, J., Ohkuri, T., Kosaka, A., Patel, P. R., McGettigan, S. E., Nace, A. K. et al., Rational development and characterization of humanized anti-EGFR variant III chimeric antigen receptor T cells for glioblastoma. Sci. Transl. Med. 2015. 7: 275ra222.
83. Ohno, M., Ohkuri, T., Kosaka, A., Tanahashi, K., June, C. H., Natsume, A. and Okada, H., Expression of miR-17-92 enhances anti-tumor activity of T-cells transduced with the anti-EGFRvIII chimeric antigen receptor in mice bearing human GBM xenografts. J. Immunother. Cancer 2013. 1: 21.
84. Legras, S., Gunthert, U., Stauder, R., Curt, F., Oliferenko, S., Kluin-Nelemans, H. C., Marie, J. P. et al., A strong expression of CD44-6v correlates with shorter survival of patients with acute myeloid leukemia. Blood 1998. 91: 3401-3413.
85. Liebisch, P., Eppinger, S., Schopflin, C., Stehle, G., Munzert, G., Dohner, H. and Schmid, M., CD44v6, a target for novel antibody treatment approaches, is frequently expressed in multiple myeloma and associated with deletion of chromosome arm 13q. Haematologica 2005. 90: 489-493.
86. Gansauge, F., Gansauge, S., Zobywalski, A., Scharnweber, C., Link, K. H., Nussler, A. K. and Beger, H. G., Differential expression of CD44 splice variants in human pancreatic adenocarcinoma and in normal pancreas. Cancer Res. 1995. 55: 5499-5503.
87. Casucci, M., Nicolis di Robilant, B., Falcone, L., Camisa, B., Norelli, M., Genovese, P., Gentner, B. et al., CD44v6-targeted T cells mediate potent antitumor effects against acute myeloid leukemia and multiple myeloma. Blood 2014. 122: 3461-3472.
88. Di Stasi, A., Tey, S. K., Dotti, G., Fujita, Y., Kennedy-Nasser, A., Martinez, C., Straathof, K. et al., Inducible apoptosis as a safety switch for adoptive cell therapy. N. Engl. J. Med. 2011. 365: 1673-1683.
89. Chang, J. T., Wherry, E. J. and Goldrath, A. W., Molecular regulation of effector and memory T cell differentiation. Nat. Immunol. 2014. 15: 1104-1115.
90. Dudley, M. E., Gross, C. A., Langhan, M. M., Garcia, M. R., Sherry, R. M., Yang, J. C., Phan, G. Q. et al., CD8+ enriched "young" tumor infiltrating lymphocytes can mediate regression of metastatic melanoma. Clin. Cancer Res. 2010. 16: 6122-6131.
91. Kaneko, S., Mastaglio, S., Bondanza, A., Ponzoni, M., Sanvito, F., Aldrighetti, L., Radrizzani, M. et al., IL-7 and IL-15 allow the generation of suicide gene-modified alloreactive self-renewing central memory human T lymphocytes. Blood 2009. 113: 1006-1015.
92. Bondanza, A., Hambach, L., Aghai, Z., Nijmeijer, B., Kaneko, S., Mastaglio, S., Radrizzani, M. et al., IL-7 receptor expression identifies suicide gene-modified allospecific CD8+ T cells capable of self-renewal and differentiation into antileukemia effectors. Blood 2011. 117: 6469-6478.
93. Cieri, N., Camisa, B., Cocchiarella, F., Forcato, M., Oliveira, G., Provasi, E., Bondanza, A. et al., IL-7 and IL-15 instruct the generation of human memory stem T cells from naive precursors. Blood 2013. 121: 573-584.
94. Gattinoni, L., Lugli, E., Ji, Y., Pos, Z., Paulos, C. M., Quigley, M. F., Almeida, J. R. et al., A human memory T cell subset with stem cell-like properties. Nat. Med. 2011. 17: 1290-1297.
95. Lugli, E., Dominguez, M. H., Gattinoni, L., Chattopadhyay, P. K., Bolton, D. L., Song, K., Klatt, N. R. et al., Superior T memory stem cell persistence supports long-lived T cell memory. J. Clin. Invest. 2013. 123: 594-599.
96. Cieri, N., Oliveira, G., Greco, R., Forcato, M., Taccioli, C., Cianciotti, B., Valtolina, V. et al., Generation of human memory stem T cells upon haploidentical T-replete hematopoietic stem cell transplantation. Blood 2015.
97. Biasco, L., Scala, S., Basso Ricci, L., Dionisio, F., Baricordi, C., Calabria, A., Giannelli, S. et al., In vivo tracking of T cells in humans unveils decade-long survival and activity of genetically modified T memory stem cells. Sci. Transl. Med. 2015. 7: 273ra213.
98. Xu, Y., Zhang, M., Ramos, C. A., Durett, A., Liu, E., Dakhova, O., Liu, H. et al., Closely related T-memory stem cells correlate with in vivo expansion of CAR.CD19-T cells and are preserved by IL-7 and IL-15. Blood 2014. 123: 3750-3759.
99. Klebanoff, C. A., Gattinoni, L. and Restifo, N. P., Sorting through subsets: which T-cell populations mediate highly effective adoptive immunotherapy? J. Immunother. 2012. 35: 651-660.
100. Gattinoni, L., Zhong, X. S., Palmer, D. C., Ji, Y., Hinrichs, C. S., Yu, Z., Wrzesinski, C. et al., Wnt signaling arrests effector T cell differentiation and generates CD8+ memory stem cells. Nat. Med. 2009. 15: 808-813.
101. Powell, J. D. and Delgoffe, G. M., The mammalian target of rapamycin: linking T cell differentiation, function, and metabolism. Immunity 2010. 33: 301-311.
102. Crompton, J. G., Sukumar, M., Roychoudhuri, R., Clever, D., Gros, A., Eil, R. L., Tran, E. et al., Akt inhibition enhances expansion of potent tumor-specific lymphocytes with memory cell characteristics. Cancer Res. 2014. 75: 296-305.
103. van der Waart, A. B., van de Weem, N. M., Maas, F., Kramer, C. S., Kester, M. G., Falkenburg, J. H., Schaap, N. et al., Inhibition of Akt signaling promotes the generation of superior tumor-reactive T cells for adoptive immunotherapy. Blood 2014. 124: 3490-3500.
104. Dhodapkar, M. V. and Richter, J., Harnessing natural killer T (NKT) cells in human myeloma: progress and challenges. Clin. Immunol. 2011. 140: 160-166.
105. Lepore, M., de Lalla, C., Gundimeda, S. R., Gsellinger, H., Consonni, M., Garavaglia, C., Sansano, S. et al., A novel self-lipid antigen targets human T cells against CD1c(+) leukemias. J. Exp. Med. 2014. 211: 1363-1377.
106. Heczey, A., Liu, D., Tian, G., Courtney, A. N., Wei, J., Marinova, E., Gao, X. et al., Invariant NKT cells with chimeric antigen receptor provide a novel platform for safe and effective cancer immunotherapy. Blood 2014. 124: 2824-2833.
107. Deniger, D. C., Switzer, K., Mi, T., Maiti, S., Hurton, L., Singh, H., Huls, H. et al., Bispecific T-cells expressing polyclonal repertoire of endogenous gammadelta T-cell receptors and introduced CD19-specific chimeric antigen receptor. Mol. Ther. 2013. 21: 638-647.
108. Stromnes, I. M., Blattman, J. N., Tan, X., Jeevanjee, S., Gu, H. and Greenberg, P. D., Abrogating Cbl-b in effector CD8(+) T cells improves the efficacy of adoptive therapy of leukemia in mice. J. Clin. Invest. 2010. 120: 3722-3734.
109. Hinterleitner, R., Gruber, T., Pfeifhofer-Obermair, C., Lutz-Nicoladoni, C., Tzankov, A., Schuster, M., Penninger, J. M. et al., Adoptive transfer of siRNA Cblb-silenced CD8+ T lymphocytes augments tumor vaccine efficacy in a B16 melanoma model. PLoS One 2012. 7: e44295.
110. Foster, A. E., Dotti, G., Lu, A., Khalil, M., Brenner, M. K., Heslop, H. E., Rooney, C. M. et al., Antitumor activity of EBV-specific T lymphocytes transduced with a dominant negative TGF-beta receptor. J. Immunother. 2008. 31: 500-505.
111. Bendle, G. M., Linnemann, C., Bies, L., Song, J. Y. and Schumacher, T. N., Blockade of TGF-beta signaling greatly enhances the efficacy of TCR gene therapy of cancer. J. Immunol. 2013. 191: 3232-3239.
112. Hebeisen, M., Baitsch, L., Presotto, D., Baumgaertner, P., Romero, P., Michielin, O., Speiser, D. E. et al., SHP-1 phosphatase activity counteracts increased T cell receptor affinity. J. Clin. Invest. 2013. 123: 1044-1056.
113. Caruana, I., Savoldo, B., Hoyos, V., Weber, G., Liu, H., Kim, E. S., Ittmann, M. M. et al., Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T lymphocytes. Nat. Med. 2015. 21: 524-529.
114. Chmielewski, M., Hombach, A. A. and Abken, H., Of CARs and TRUCKs: chimeric antigen receptor (CAR) T cells engineered with an inducible cytokine to modulate the tumor stroma. Immunol. Rev. 2014. 257: 83-90.
115. Hoyos, V., Savoldo, B., Quintarelli, C., Mahendravada, A., Zhang, M., Vera, J., Heslop, H. E. et al., Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/leukemia effects and safety. Leukemia 2010. 24: 1160-1170.
116. Pegram, H. J., Purdon, T. J., van Leeuwen, D. G., Curran, K. J., Giralt, S. A., Barker, J. N. and Brentjens, R. J., IL-12-secreting CD19-targeted cord blood-derived T cells for the immunotherapy of B-cell acute lymphoblastic leukemia. Leukemia 2015. 29: 415-422.
117. Perna, S. K., Savoldo, B. and Dotti, G., Genetic modification of cytotoxic T lymphocytes to express cytokine receptors. Methods Mol. Biol. 2014. 1139: 189-200.
118. Di Stasi, A., De Angelis, B., Rooney, C. M., Zhang, L., Mahendravada, A., Foster, A. E., Heslop, H. E. et al., T lymphocytes coexpressing CCR4 and a chimeric antigen receptor targeting CD30 have improved homing and antitumor activity in a Hodgkin tumor model. Blood 2009. 113: 6392-6402.
119. Peng, W., Ye, Y., Rabinovich, B. A., Liu, C., Lou, Y., Zhang, M., Whittington, M. et al., Transduction of tumor-specific T cells with CXCR2 chemokine receptor improves migration to tumor and antitumor immune responses. Clin. Cancer Res. 2010. 16: 5458-5468.
120. Chodon, T., Comin-Anduix, B., Chmielowski, B., Koya, R. C., Wu, Z., Auerbach, M., Ng, C. et al., Adoptive transfer of MART-1 T-cell receptor transgenic lymphocytes and dendritic cell vaccination in patients with metastatic melanoma. Clin. Cancer Res. 2014. 20: 2457-2465.
121. Pardoll, D. M., The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer 2012. 12: 252-264.
122. Siska, P. J. and Rathmell, J. C., T cell metabolic fitness in antitumor immunity. Trends Immunol. 2015.
123. John, L. B., Devaud, C., Duong, C. P., Yong, C. S., Beavis, P. A., Haynes, N. M., Chow, M. T. et al., Anti-PD-1 antibody therapy potently enhances the eradication of established tumors by gene-modified T cells. Clin. Cancer Res. 2013. 19: 5636-5646.
124. Rosenberg, S. A., IL-2: the first effective immunotherapy for human cancer. J. Immunol. 2014. 192: 5451-5458.
125. Rosenberg, S. A., Restifo, N. P., Yang, J. C., Morgan, R. A. and Dudley, M. E., Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nat. Rev. Cancer 2008. 8: 299-308.
126. Rosenberg, S. A., Sportes, C., Ahmadzadeh, M., Fry, T. J., Ngo, L. T., Schwarz, S. L., Stetler-Stevenson, M. et al., IL-7 administration to humans leads to expansion of CD8+ and CD4+ cells but a relative decrease of CD4+ T-regulatory cells. J. Immunother. 2006. 29: 313-319.
127. Conlon, K. C., Lugli, E., Welles, H. C., Rosenberg, S. A., Fojo, A. T., Morris, J. C., Fleisher, T. A. et al., Redistribution, hyperproliferation, activation of natural killer cells and CD8 T cells, and cytokine production during first-in-human clinical trial of recombinant human interleukin-15 in patients with cancer. J. Clin. Oncol. 2015. 33: 74-82.
128. Bellone, M., Mondino, A. and Corti, A., Vascular targeting, chemotherapy and active immunotherapy: teaming up to attack cancer. Trends Immunol. 2008. 29: 235-241.
129. Bellone, M., Calcinotto, A. and Corti, A., Won't you come on in? How to favor lymphocyte infiltration in tumors. Oncoimmunology 2013. 1: 986-988.
130. Calcinotto, A., Grioni, M., Jachetti, E., Curnis, F., Mondino, A., Parmiani, G., Corti, A. et al., Targeting TNF-alpha to neoangiogenic vessels enhances lymphocyte infiltration in tumors and increases the therapeutic potential of immunotherapy. J. Immunol. 2012. 188: 2687-2694.
131. Johansson, A., Hamzah, J., Payne, C. J. and Ganss, R., Tumor-targeted TNFalpha stabilizes tumor vessels and enhances active immunotherapy. Proc. Natl. Acad. Sci. USA 2011. 109: 7841-7846.
132. Reuss, S., Sebestyen, Z., Heinz, N., Loew, R., Baum, C., Debets, R. and Uckert, W., TCR-engineered T cells: a model of inducible TCR expression to dissect the interrelationship between two TCRs. Eur. J. Immunol. 2014. 44: 265-274.
133. Xu, Y., Hyun, Y. M., Lim, K., Lee, H., Cummings, R. J., Gerber, S. A., Bae, S. et al., Optogenetic control of chemokine receptor signal and T-cell migration. Proc. Natl. Acad. Sci. USA 2014. 111: 6371-6376.