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Principles of adoptive T cell therapy in cancer

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Abstract

Adoptive cell therapy (ACT) utilizing either tumor-infiltrating lymphocyte (TIL)-derived T cells or T cells genetically engineered to express tumor recognizing receptors has emerged as a powerful and potentially curative therapy for several cancers. Many ACT-based therapies have recently entered late-phase clinical testing, with several T cell therapies already achieving regulatory approval for the treatment of patients with B cell malignancies. In this review, we briefly outline the principles of adoptively transferred T cells for the treatment of cancer.

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Reference

  1. Leach DR, Krummel MF, Allison JP (1996) Enhancement of antitumor immunity by CTLA-4 blockade. Science 271:1734–1736

    Article  CAS  PubMed  Google Scholar 

  2. Ishida Y, Agata Y, Shibahara K, Honjo T (1992) Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J 11:3887–3895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, Fitz LJ, Malenkovich N, Okazaki T, Byrne MC, Horton HF, Fouser L, Carter L, Ling V, Bowman MR, Carreno BM, Collins M, Wood CR, Honjo T (2000) Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 192:1027–1034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hodi FS, O'Day SJ, McDermott DF et al (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363:711–723

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, Hassel JC, Rutkowski P, McNeil C, Kalinka-Warzocha E, Savage KJ, Hernberg MM, Lebbé C, Charles J, Mihalcioiu C, Chiarion-Sileni V, Mauch C, Cognetti F, Arance A, Schmidt H, Schadendorf D, Gogas H, Lundgren-Eriksson L, Horak C, Sharkey B, Waxman IM, Atkinson V, Ascierto PA (2015) Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 372:320–330

    Article  CAS  PubMed  Google Scholar 

  6. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, Ferrucci PF, Hill A, Wagstaff J, Carlino MS, Haanen JB, Maio M, Marquez-Rodas I, McArthur GA, Ascierto PA, Long GV, Callahan MK, Postow MA, Grossmann K, Sznol M, Dreno B, Bastholt L, Yang A, Rollin LM, Horak C, Hodi FS, Wolchok JD (2015) Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 373:23–34

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L, Carcereny E, Ahn MJ, Felip E, Lee JS, Hellmann MD, Hamid O, Goldman JW, Soria JC, Dolled-Filhart M, Rutledge RZ, Zhang J, Lunceford JK, Rangwala R, Lubiniecki GM, Roach C, Emancipator K, Gandhi L, KEYNOTE-001 Investigators (2015) Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 372:2018–2028

    Article  PubMed  Google Scholar 

  8. Sharma P, Callahan MK, Bono P, Kim J, Spiliopoulou P, Calvo E, Pillai RN, Ott PA, de Braud F, Morse M, le DT, Jaeger D, Chan E, Harbison C, Lin CS, Tschaika M, Azrilevich A, Rosenberg JE (2016) Nivolumab monotherapy in recurrent metastatic urothelial carcinoma (CheckMate 032): a multicentre, open-label, two-stage, multi-arm, phase 1/2 trial. Lancet Oncol 17:1590–1598

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Bauml J, Seiwert TY, Pfister DG, Worden F, Liu SV, Gilbert J, Saba NF, Weiss J, Wirth L, Sukari A, Kang H, Gibson MK, Massarelli E, Powell S, Meister A, Shu X, Cheng JD, Haddad R (2017) Pembrolizumab for platinum- and cetuximab-refractory head and neck cancer: results from a single-arm, phase II study. J Clin Oncol 35:1542–1549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, Schuster SJ, Millenson MM, Cattry D, Freeman GJ, Rodig SJ, Chapuy B, Ligon AH, Zhu L, Grosso JF, Kim SY, Timmerman JM, Shipp MA, Armand P (2015) PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med 372:311–319

    Article  CAS  PubMed  Google Scholar 

  11. Sharma P, Allison JP (2015) The future of immune checkpoint therapy. Science 348:56–61

    Article  CAS  PubMed  Google Scholar 

  12. Rosenberg SA, Fox E, Churchill WH (1972) Spontaneous regression of hepatic metastases from gastric carcinoma. Cancer 29:472–474

    Article  CAS  PubMed  Google Scholar 

  13. Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, Jungbluth AA, Frosina D, Gnjatic S, Ambrosone C, Kepner J, Odunsi T, Ritter G, Lele S, Chen YT, Ohtani H, Old LJ, Odunsi K (2005) Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci U S A 102:18538–18543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Loi S, Sirtaine N, Piette F, Salgado R, Viale G, van Eenoo F, Rouas G, Francis P, Crown JPA, Hitre E, de Azambuja E, Quinaux E, di Leo A, Michiels S, Piccart MJ, Sotiriou C (2013) Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy: BIG 02-98. J Clin Oncol 31:860–867

    Article  CAS  PubMed  Google Scholar 

  15. Clemente CG, Mihm MC Jr, Bufalino R et al (1996) Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma. Cancer 77:1303–1310

    Article  CAS  PubMed  Google Scholar 

  16. Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pagès C, Tosolini M, Camus M, Berger A, Wind P, Zinzindohoué F, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Pagès F (2006) Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313:1960–1964

    Article  CAS  PubMed  Google Scholar 

  17. Smith KA, Gilbride KJ, Favata MF (1980) Lymphocyte activating factor promotes T-cell growth factor production by cloned murine lymphoma cells. Nature 287:853–855

    Article  CAS  PubMed  Google Scholar 

  18. Rosenberg SA, Packard BS, Aebersold PM, Solomon D, Topalian SL, Toy ST, Simon P, Lotze MT, Yang JC, Seipp CA, Simpson C, Carter C, Bock S, Schwartzentruber D, Wei JP, White DE (1988) Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. N Engl J Med 319:1676–1680

    Article  CAS  PubMed  Google Scholar 

  19. Svane IM, Donia M, Met Ö (2018) Adoptive T Cell Therapy. In: Haanen JBAG, Califano R, Lugowska I, Garassino MC (eds) Handbook of Immuno-Oncology, ESMO, Lugano, p 15–22

  20. Dudley ME, Wunderlich JR, Shelton TE, Even J, Rosenberg SA (2003) Generation of tumor-infiltrating lymphocyte cultures for use in adoptive transfer therapy for melanoma patients. J Immunother 26:332–342

    Article  PubMed  PubMed Central  Google Scholar 

  21. Dudley ME, Wunderlich JR, Yang JC, Sherry RM, Topalian SL, Restifo NP, Royal RE, Kammula U, White DE, Mavroukakis SA, Rogers LJ, Gracia GJ, Jones SA, Mangiameli DP, Pelletier MM, Gea-Banacloche J, Robinson MR, Berman DM, Filie AC, Abati A, Rosenberg SA (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

    Article  CAS  PubMed  Google Scholar 

  22. Andersen R, Borch TH, Draghi A, Gokuldass A, Rana MAH, Pedersen M, Nielsen M, Kongsted P, Kjeldsen JW, Westergaard MCW, Radic HD, Chamberlain CA, Hölmich LR, Hendel HW, Larsen MS, Met Ö, Svane IM, Donia M (2018) T cells isolated from patients with checkpoint inhibitor resistant-melanoma are functional and can mediate tumor regression. Ann Oncol 29(7):1575–1581

  23. Tran KQ, Zhou J, Durflinger KH, Langhan MM, Shelton TE, Wunderlich JR, Robbins PF, Rosenberg SA, Dudley ME (2008) Minimally cultured tumor-infiltrating lymphocytes display optimal characteristics for adoptive cell therapy. J Immunother 31:742–751

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Donia M, Junker N, Ellebaek E, Andersen MH, Straten PT, Svane IM (2012) Characterization and comparison of ‘standard’ and ‘young’ tumour-infiltrating lymphocytes for adoptive cell therapy at a Danish translational research institution. Scand J Immunol 75:157–167

    Article  CAS  PubMed  Google Scholar 

  25. Besser MJ, Shapira-Frommer R, Treves AJ, Zippel D, Itzhaki O, Schallmach E, Kubi A, Shalmon B, Hardan I, Catane R, Segal E, Markel G, Apter S, Nun AB, Kuchuk I, Shimoni A, Nagler A, Schachter J (2009) Minimally cultured or selected autologous tumor-infiltrating lymphocytes after a lympho-depleting chemotherapy regimen in metastatic melanoma patients. J Immunother 32:415–423

    Article  CAS  PubMed  Google Scholar 

  26. Klebanoff CA, Khong HT, Antony PA, Palmer DC, Restifo NP (2005) Sinks, suppressors and antigen presenters: how lymphodepletion enhances T cell-mediated tumor immunotherapy. Trends Immunol 26:111–117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ, Topalian SL, Sherry R, Restifo NP, Hubicki AM, Robinson MR, Raffeld M, Duray P, Seipp CA, Rogers-Freezer L, Morton KE, Mavroukakis SA, White DE, Rosenberg SA (2002) Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 298:850–854

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Itzhaki O, Hovav E, Ziporen Y, Levy D, Kubi A, Zikich D, Hershkovitz L, Treves AJ, Shalmon B, Zippel D, Markel G, Shapira-Frommer R, Schachter J, Besser MJ (2011) Establishment and large-scale expansion of minimally cultured “young” tumor infiltrating lymphocytes for adoptive transfer therapy. J Immunother 34:212–220

    Article  PubMed  Google Scholar 

  29. Radvanyi LG, Bernatchez C, Zhang M, Fox PS, Miller P, Chacon J, Wu R, Lizee G, Mahoney S, Alvarado G, Glass M, Johnson VE, McMannis JD, Shpall E, Prieto V, Papadopoulos N, Kim K, Homsi J, Bedikian A, Hwu WJ, Patel S, Ross MI, Lee JE, Gershenwald JE, Lucci A, Royal R, Cormier JN, Davies MA, Mansaray R, Fulbright OJ, Toth C, Ramachandran R, Wardell S, Gonzalez A, Hwu P (2012) Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients. Clin Cancer Res 18:6758–6770

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Andersen R, Donia M, Ellebaek E, Borch TH, Kongsted P, Iversen TZ, Ho lmich LR, Hendel HW, Met O, Andersen MH, thor Straten P, Svane IM (2016) Long-lasting complete responses in patients with metastatic melanoma after adoptive cell therapy with tumor-infiltrating lymphocytes and an attenuated IL2 regimen. Clin Cancer Res 22:3734–3745

    Article  CAS  PubMed  Google Scholar 

  31. Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM, Royal RE, Topalian SL, Kammula US, Restifo NP, Zheng Z, Nahvi A, de Vries CR, Rogers-Freezer LJ, Mavroukakis SA, Rosenberg SA (2006) Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 314:126–129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Johnson LA, Morgan RA, Dudley ME, Cassard L, Yang JC, Hughes MS, Kammula US, Royal RE, Sherry RM, Wunderlich JR, Lee CCR, Restifo NP, Schwarz SL, Cogdill AP, Bishop RJ, Kim H, Brewer CC, Rudy SF, VanWaes C, Davis JL, Mathur A, Ripley RT, Nathan DA, Laurencot CM, Rosenberg SA (2009) Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. Blood 114:535–546

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Robbins PF, Morgan RA, Feldman SA, Yang JC, Sherry RM, Dudley ME, Wunderlich JR, Nahvi AV, Helman LJ, Mackall CL, Kammula US, Hughes MS, Restifo NP, Raffeld M, Lee CCR, Levy CL, Li YF, el-Gamil M, Schwarz SL, Laurencot C, Rosenberg SA (2011) Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol 29:917–924

    Article  PubMed  PubMed Central  Google Scholar 

  34. Rapoport AP, Stadtmauer EA, Binder-Scholl GK, Goloubeva O, Vogl DT, Lacey SF, Badros AZ, Garfall A, Weiss B, Finklestein J, Kulikovskaya I, Sinha SK, Kronsberg S, Gupta M, Bond S, Melchiori L, Brewer JE, Bennett AD, Gerry AB, Pumphrey NJ, Williams D, Tayton- Martin HK, Ribeiro L, Holdich T, Yanovich S, Hardy N, Yared J, Kerr N, Philip S, Westphal S, Siegel DL, Levine BL, Jakobsen BK, Kalos M, June CH (2015) NY-ESO-1-specific TCR-engineered T cells mediate sustained antigen-specific antitumor effects in myeloma. Nat Med 21:914–921

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Davila ML, Riviere I, Wang X et al (2014) Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med 6:224ra25

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, Chew A, Gonzalez VE, Zheng Z, Lacey SF, Mahnke YD, Melenhorst JJ, Rheingold SR, Shen A, Teachey DT, Levine BL, June CH, Porter DL, Grupp SA (2014) Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med 371:1507–1517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, Bader P, Verneris MR, Stefanski HE, Myers GD, Qayed M, de Moerloose B, Hiramatsu H, Schlis K, Davis KL, Martin PL, Nemecek ER, Yanik GA, Peters C, Baruchel A, Boissel N, Mechinaud F, Balduzzi A, Krueger J, June CH, Levine BL, Wood P, Taran T, Leung M, Mueller KT, Zhang Y, Sen K, Lebwohl D, Pulsipher MA, Grupp SA (2018) Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med 378:439–448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Kochenderfer JN, Dudley ME, Kassim SH, Somerville RPT, Carpenter RO, Stetler-Stevenson M, Yang JC, Phan GQ, Hughes MS, Sherry RM, Raffeld M, Feldman S, Lu L, Li YF, Ngo LT, Goy A, Feldman T, Spaner DE, Wang ML, Chen CC, Kranick SM, Nath A, Nathan DAN, Morton KE, Toomey MA, Rosenberg SA (2015) Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor. J Clin Oncol 33:540–549

    Article  CAS  PubMed  Google Scholar 

  39. Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY (2017) Axicabtagene Ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med 377:2531–2544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Porter DL, Hwang WT, Frey NV et al (2015) Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med 7:303ra139

    Article  PubMed  PubMed Central  Google Scholar 

  41. Turtle CJ, Hay KA, Hanafi LA, Li D, Cherian S, Chen X, Wood B, Lozanski A, Byrd JC, Heimfeld S, Riddell SR, Maloney DG (2017) Durable molecular remissions in chronic lymphocytic leukemia treated with CD19-specific chimeric antigen receptor-modified T cells after failure of ibrutinib. J Clin Oncol 35:3010–3020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Brudno JN, Maric I, Hartman SD et al (2018) T cells genetically modified to express an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of poor-prognosis relapsed multiple myeloma. J Clin Oncol 36(22):2267–2280

  43. Garbe C (1993) Chemotherapy and chemoimmunotherapy in disseminated malignant melanoma. Melanoma Res 3:291–299

    CAS  PubMed  Google Scholar 

  44. Besser MJ, Shapira-Frommer R, Itzhaki O, Treves AJ, Zippel DB, Levy D, Kubi A, Shoshani N, Zikich D, Ohayon Y, Ohayon D, Shalmon B, Markel G, Yerushalmi R, Apter S, Ben-Nun A, Ben-Ami E, Shimoni A, Nagler A, Schachter J (2013) Adoptive transfer of tumor-infiltrating lymphocytes in patients with metastatic melanoma: intent-to-treat analysis and efficacy after failure to prior immunotherapies. Clin Cancer Res 19:4792–4800

    Article  CAS  PubMed  Google Scholar 

  45. Pilon-Thomas S, Kuhn L, Ellwanger S, Janssen W, Royster E, Marzban S, Kudchadkar R, Zager J, Gibney G, Sondak VK, Weber J, Mulé JJ, Sarnaik AA (2012) Efficacy of adoptive cell transfer of tumor-infiltrating lymphocytes after lymphopenia induction for metastatic melanoma. J Immunother 35:615–620

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Rosenberg SA, Yang JC, Sherry RM, Kammula US, Hughes MS, Phan GQ, Citrin DE, Restifo NP, Robbins PF, Wunderlich JR, Morton KE, Laurencot CM, Steinberg SM, White DE, Dudley ME (2011) Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res 17:4550–4557

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Goff SL, Dudley ME, Citrin DE, Somerville RP, Wunderlich JR, Danforth DN, Zlott DA, Yang JC, Sherry RM, Kammula US, Klebanoff CA, Hughes MS, Restifo NP, Langhan MM, Shelton TE, Lu L, Kwong MLM, Ilyas S, Klemen ND, Payabyab EC, Morton KE, Toomey MA, Steinberg SM, White DE, Rosenberg SA (2016) Randomized, prospective evaluation comparing intensity of Lymphodepletion before adoptive transfer of tumor-infiltrating lymphocytes for patients with metastatic melanoma. J Clin Oncol 34:2389–2397

    Article  PubMed  PubMed Central  Google Scholar 

  48. Lauss M, Donia M, Harbst K, Andersen R, Mitra S, Rosengren F, Salim M, Vallon-Christersson J, Törngren T, Kvist A, Ringnér M, Svane IM, Jönsson G (2017) Mutational and putative neoantigen load predict clinical benefit of adoptive T cell therapy in melanoma. Nat Commun 8:1738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Webb JR, Milne K, Watson P, Deleeuw RJ, Nelson BH (2014) Tumor-infiltrating lymphocytes expressing the tissue resident memory marker CD103 are associated with increased survival in high-grade serous ovarian cancer. Clin Cancer Res 20:434–444

    Article  CAS  PubMed  Google Scholar 

  50. Hilders CG, Ras L, van Eendenburg JD, Nooyen Y, Fleuren GJ (1994) Isolation and characterization of tumor-infiltrating lymphocytes from cervical carcinoma. Int J Cancer 57:805–813

    Article  CAS  PubMed  Google Scholar 

  51. Yannelli JR, Hyatt C, McConnell S, Hines K, Jacknin L, Parker L, Sanders M, Rosenberg SA (1996) Growth of tumor-infiltrating lymphocytes from human solid cancers: summary of a 5-year experience. Int J Cancer 65:413–421

    Article  CAS  PubMed  Google Scholar 

  52. Turcotte S, Gros A, Hogan K, Tran E, Hinrichs CS, Wunderlich JR, Dudley ME, Rosenberg SA (2013) Phenotype and function of T cells infiltrating visceral metastases from gastrointestinal cancers and melanoma: implications for adoptive cell transfer therapy. J Immunol 191:2217–2225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Andersen R, Westergaard MCW, Kjeldsen JW, Müller A, Pedersen NW, Hadrup SR, Met Ö, Seliger B, Kromann-Andersen B, Hasselager T, Donia M, Svane IM (2018) T-cell responses in the microenvironment of primary renal cell carcinoma-implications for adoptive cell therapy. Cancer Immunol Res 6:222–235

    Article  CAS  PubMed  Google Scholar 

  54. Zacharakis N, Chinnasamy H, Black M, Xu H, Lu YC, Zheng Z, Pasetto A, Langhan M, Shelton T, Prickett T, Gartner J, Jia L, Trebska-McGowan K, Somerville RP, Robbins PF, Rosenberg SA, Goff SL, Feldman SA (2018) Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer. Nat Med 24:724–730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Tran E, Ahmadzadeh M, Lu YC, Gros A, Turcotte S, Robbins PF, Gartner JJ, Zheng Z, Li YF, Ray S, Wunderlich JR, Somerville RP, Rosenberg SA (2015) Immunogenicity of somatic mutations in human gastrointestinal cancers. Science 350:1387–1390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Zhao Y, Zheng Z, Cohen CJ, Gattinoni L, Palmer DC, Restifo NP, Rosenberg SA, Morgan RA (2006) High-efficiency transfection of primary human and mouse T lymphocytes using RNA electroporation. Mol Ther 13:151–159

    Article  CAS  PubMed  Google Scholar 

  57. Clay TM, Custer MC, Sachs J et al (1999) Efficient transfer of a tumor antigen-reactive TCR to human peripheral blood lymphocytes confers anti-tumor reactivity. J Immunol 163:507–513

    CAS  PubMed  Google Scholar 

  58. Tsuji T, Yasukawa M, Matsuzaki J, Ohkuri T, Chamoto K, Wakita D, Azuma T, Niiya H, Miyoshi H, Kuzushima K, Oka Y, Sugiyama H, Ikeda H, Nishimura T (2005) Generation of tumor-specific, HLA class I-restricted human Th1 and Tc1 cells by cell engineering with tumor peptide-specific T-cell receptor genes. Blood 106:470–476

    Article  CAS  PubMed  Google Scholar 

  59. Peng PD, Cohen CJ, Yang S, Hsu C, Jones S, Zhao Y, Zheng Z, Rosenberg SA, Morgan RA (2009) Efficient nonviral sleeping beauty transposon-based TCR gene transfer to peripheral blood lymphocytes confers antigen-specific antitumor reactivity. Gene Ther 16:1042–1049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Eyquem J, Mansilla-Soto J, Giavridis T, van der Stegen SJC, Hamieh M, Cunanan KM, Odak A, Gönen M, Sadelain M (2017) Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection. Nature 543:113–117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Robbins PF, Li YF, El-Gamil M et al (2008) Single and dual amino acid substitutions in TCR CDRs can enhance antigen-specific T cell functions. J Immunol 180:6116–6131

    Article  CAS  PubMed  Google Scholar 

  62. Stanislawski T, Voss RH, Lotz C, Sadovnikova E, Willemsen RA, Kuball J, Ruppert T, Bolhuis RLH, Melief CJ, Huber C, Stauss HJ, Theobald M (2001) Circumventing tolerance to a human MDM2-derived tumor antigen by TCR gene transfer. Nat Immunol 2:962–970

    Article  CAS  PubMed  Google Scholar 

  63. de Witte MA, Coccoris M, Wolkers MC, van den Boom M, Mesman EM, Song JY, van der Valk M, Haanen JB, Schumacher TN (2006) Targeting self-antigens through allogeneic TCR gene transfer. Blood 108:870–877

    Article  CAS  PubMed  Google Scholar 

  64. Linette GP, Stadtmauer EA, Maus MV, Rapoport AP, Levine BL, Emery L, Litzky L, Bagg A, Carreno BM, Cimino PJ, Binder-Scholl GK, Smethurst DP, Gerry AB, Pumphrey NJ, Bennett AD, Brewer JE, Dukes J, Harper J, Tayton-Martin HK, Jakobsen BK, Hassan NJ, Kalos M, June CH (2013) Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma. Blood 122:863–871

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Kageyama S, Ikeda H, Miyahara Y, Imai N, Ishihara M, Saito K, Sugino S, Ueda S, Ishikawa T, Kokura S, Naota H, Ohishi K, Shiraishi T, Inoue N, Tanabe M, Kidokoro T, Yoshioka H, Tomura D, Nukaya I, Mineno J, Takesako K, Katayama N, Shiku H (2015) Adoptive transfer of MAGE-A4 T-cell receptor gene-transduced lymphocytes in patients with recurrent esophageal cancer. Clin Cancer Res 21:2268–2277

    Article  CAS  PubMed  Google Scholar 

  66. Parkhurst MR, Yang JC, Langan RC, Dudley ME, Nathan DAN, Feldman SA, Davis JL, Morgan RA, Merino MJ, Sherry RM, Hughes MS, Kammula US, Phan GQ, Lim RM, Wank SA, Restifo NP, Robbins PF, Laurencot CM, Rosenberg SA (2011) T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis. Mol Ther 19:620–626

    Article  CAS  PubMed  Google Scholar 

  67. Casucci M, Hawkins RE, Dotti G, Bondanza A (2015) Overcoming the toxicity hurdles of genetically targeted T cells. Cancer Immunol Immunother 64:123–130

    Article  CAS  PubMed  Google Scholar 

  68. Kershaw MH, Westwood JA, Parker LL, Wang G, Eshhar Z, Mavroukakis SA, White DE, Wunderlich JR, Canevari S, Rogers-Freezer L, Chen CC, Yang JC, Rosenberg SA, Hwu P (2006) A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer. Clin Cancer Res 12:6106–6115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Kalos M, Levine BL, Porter DL et al (2011) T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med 3:95ra73

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Turtle CJ, Hanafi LA, Berger C et al (2016) Immunotherapy of non-Hodgkin’s lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified T cells. Sci Transl Med 8:355ra116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Park JH, Riviere I, Gonen M et al (2018) Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. N Engl J Med 378:449–459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA, Fry TJ, Orentas R, Sabatino M, Shah NN, Steinberg SM, Stroncek D, Tschernia N, Yuan C, Zhang H, Zhang L, Rosenberg SA, Wayne AS, Mackall CL (2015) T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet 385:517–528

    Article  CAS  PubMed  Google Scholar 

  73. Turtle CJ, Hanafi LA, Berger C, Gooley TA, Cherian S, Hudecek M, Sommermeyer D, Melville K, Pender B, Budiarto TM, Robinson E, Steevens NN, Chaney C, Soma L, Chen X, Yeung C, Wood B, Li D, Cao J, Heimfeld S, Jensen MC, Riddell SR, Maloney DG (2016) CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients. J Clin Invest 126:2123–2138

    Article  PubMed  PubMed Central  Google Scholar 

  74. Srivastava S, Riddell SR (2018) Chimeric antigen receptor T cell therapy: challenges to bench-to-bedside efficacy. J Immunol 200:459–468

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Center for Cancer Immune Therapy, Department of Hematology, Copenhagen University Hospital, Entrance 81, Floor 05, 2730, Herlev, Denmark

    Özcan Met, Kasper Mølgaard Jensen, Christopher Aled Chamberlain, Marco Donia & Inge Marie Svane

  2. Department of Oncology, Copenhagen University Hospital, Herlev, Denmark

    Özcan Met, Marco Donia & Inge Marie Svane

  3. Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Özcan Met

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  1. Özcan Met
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  2. Kasper Mølgaard Jensen
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  3. Christopher Aled Chamberlain
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  4. Marco Donia
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  5. Inge Marie Svane
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Correspondence to Özcan Met.

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This article is a contribution to the special issue on Anti-cancer Immunotherapy: Breakthroughs and Future Strategies - Guest Editor: Mads Hald Andersen

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Met, Ö., Jensen, K.M., Chamberlain, C.A. et al. Principles of adoptive T cell therapy in cancer. Semin Immunopathol 41, 49–58 (2019). https://doi.org/10.1007/s00281-018-0703-z

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  • DOI: https://doi.org/10.1007/s00281-018-0703-z

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