Advertisement

Cancer Immunology, Immunotherapy

, Volume 67, Issue 2, pp 311–325 | Cite as

Clinical and immunologic evaluation of three metastatic melanoma patients treated with autologous melanoma-reactive TCR-transduced T cells

  • Tamson Moore
  • Courtney Regan Wagner
  • Gina M. Scurti
  • Kelli A. Hutchens
  • Constantine Godellas
  • Ann Lau Clark
  • Elizabeth Motunrayo Kolawole
  • Lance M. Hellman
  • Nishant K. Singh
  • Fernando A. Huyke
  • Siao-Yi Wang
  • Kelly M. Calabrese
  • Heather D. Embree
  • Rimas Orentas
  • Keisuke Shirai
  • Emilia Dellacecca
  • Elizabeth Garrett-Mayer
  • Mingli Li
  • Jonathan M. Eby
  • Patrick J. Stiff
  • Brian D. Evavold
  • Brian M. Baker
  • I. Caroline Le Poole
  • Boro Dropulic
  • Joseph I. Clark
  • Michael I. Nishimura
Original Article

Abstract

Malignant melanoma incidence has been increasing for over 30 years, and despite promising new therapies, metastatic disease remains difficult to treat. We describe preliminary results from a Phase I clinical trial (NCT01586403) of adoptive cell therapy in which three patients received autologous CD4+ and CD8+ T cells transduced with a lentivirus carrying a tyrosinase-specific TCR and a marker protein, truncated CD34 (CD34t). This unusual MHC Class I-restricted TCR produces functional responses in both CD4+ and CD8+ T cells. Parameters monitored on transduced T cells included activation (CD25, CD69), inhibitory (PD-1, TIM-3, CTLA-4), costimulatory (OX40), and memory (CCR7) markers. For the clinical trial, T cells were activated, transduced, selected for CD34t+ cells, then re-activated, and expanded in IL-2 and IL-15. After lymphodepleting chemotherapy, patients were given transduced T cells and IL-2, and were followed for clinical and biological responses. Transduced T cells were detected in the circulation of three treated patients for the duration of observation (42, 523, and 255 days). Patient 1 tolerated the infusion well but died from progressive disease after 6 weeks. Patient 2 had a partial response by RECIST criteria then progressed. After progressing, Patient 2 was given high-dose IL-2 and subsequently achieved complete remission, coinciding with the development of vitiligo. Patient 3 had a mixed response that did not meet RECIST criteria for a clinical response and developed vitiligo. In two of these three patients, adoptive transfer of tyrosinase-reactive TCR-transduced T cells into metastatic melanoma patients had clinical and/or biological activity without serious adverse events.

Keywords

Adoptive transfer Metastatic melanoma Clinical trial Transduced T cells Immunotherapy Vitiligo 

Abbreviations

2D

Two-dimensional

3D

Three-dimensional

CCR7

C–C motif chemokine receptor 7

CD34t

Truncated CD34

FDA

U.S. Food and Drug Administration

pMHC

Peptide-loaded MHC complexes, in this study, tyrosinase peptide-loaded HLA-A2 MHC molecules

rhIL-2

Recombinant human IL-2

rhIL-15

Recombinant human IL-15

TIM-3

T cell immunoglobulin and mucin-domain containing-3

Treg

Regulatory CD4+ T cells

Notes

Acknowledgements

All flow cytometry was performed in the Loyola University, Chicago, Flow Cytometry Core, with the assistance of Patricia Simms.

Funding

This study was funded by National Institute of Health Grants: R43 CA126461 (Boro Dropulic), R44 CA126461 (Boro Dropulic), R01 CA90873 (Michael I. Nishimura), R01 CA104947 (Michael I. Nishimura), R01 CA104947-S1 (Michael I. Nishimura), P01 CA154778 (Michael I. Nishimura), R01 AI129543-01 (Brian M. Baker, Brian D. Evavold, Michael I. Nishimura), R01 AI096879 (Brian D. Evavold).

Compliance with ethical standards

Conflict of interest

Author Joseph I. Clark received speaking honorariums from Merck and Bristol-Myers Squibb, and is an unpaid member of the steering committee for the Prometheus PROCLAIM high-dose IL-2 database. Other authors report no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

262_2017_2073_MOESM1_ESM.pdf (2.4 mb)
Supplementary material 1 (PDF 2490 kb)

References

  1. 1.
    Howlader N, Noone A, Krapcho M, Miller D, Bishop K, Kosary C, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis D, Chen H, Feuer E, Cronin K (2016) SEER Cancer Statistics Review, 1975–2014. Surveillance Research Program, National Cancer Institute Bethesda, MD. https://seer.cancer.gov/csr/1975_2014/, based on November 2016 SEER data submission, posted to the SEER web site, April 2017. Accessed 28 June 2017
  2. 2.
    Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136:E359–E386CrossRefPubMedGoogle Scholar
  3. 3.
    Pardoll DM (2012) The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12:252–264CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Postow MA, Callahan MK, Wolchok JD (2015) Immune checkpoint blockade in cancer therapy. J Clin Oncol 33:1974–1982CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Callahan MK, Postow MA, Wolchok JD (2014) CTLA-4 and PD-1 pathway blockade: combinations in the clinic. Front Oncol 4:385PubMedGoogle Scholar
  6. 6.
    Michot JM, Bigenwald C, Champiat S, Collins M, Carbonnel F, Postel-Vinay S, Berdelou A, Varga A, Bahleda R, Hollebecque A, Massard C, Fuerea A, Ribrag V, Gazzah A, Armand JP, Amellal N, Angevin E, Noel N, Boutros C, Mateus C, Robert C, Soria JC, Marabelle A, Lambotte O (2016) Immune-related adverse events with immune checkpoint blockade: a comprehensive review. Eur J Cancer 54:139–148CrossRefPubMedGoogle Scholar
  7. 7.
    Teixidó C, González-Cao M, Karachaliou N, Rosell R (2015) Predictive factors for immunotherapy in melanoma. Ann Transl Med 3:208PubMedPubMedCentralGoogle Scholar
  8. 8.
    Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, Chmielowski B, Spasic M, Henry G, Ciobanu V, West AN, Carmona M, Kivork C, Seja E, Cherry G, Gutierrez AJ, Grogan TR, Mateus C, Tomasic G, Glaspy JA, Emerson RO, Robins H, Pierce RH, Elashoff DA, Robert C, Ribas A (2014) PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 515:568–571CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Daud AI, Loo K, Pauli ML, Sanchez-Rodriguez R, Sandoval PM, Taravati K, Tsai K, Nosrati A, Nardo L, Alvarado MD, Algazi AP, Pampaloni MH, Lobach IV, Hwang J, Pierce RH, Gratz IK, Krummel MF, Rosenblum MD (2016) Tumor immune profiling predicts response to anti-PD-1 therapy in human melanoma. J Clin Invest 126:3447–3452CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Kvistborg P, Philips D, Kelderman S, Hageman L, Ottensmeier C, Joseph-Pietras D, Welters MJ, van der Burg S, Kapiteijn E, Michielin O, Romano E, Linnemann C, Speiser D, Blank C, Haanen JB, Schumacher TN (2014) Anti-CTLA-4 therapy broadens the melanoma-reactive CD8+ T cell response. Sci Transl Med 6:254ra128CrossRefPubMedGoogle Scholar
  11. 11.
    Cha E, Klinger M, Hou Y, Cummings C, Ribas A, Faham M, Fong L (2014) Improved survival with T cell clonotype stability after anti-CTLA-4 treatment in cancer patients. Sci Transl Med 6:238ra270CrossRefGoogle Scholar
  12. 12.
    Roszkowski JJ, Lyons GE, Kast WM, Yee C, Van Besien K, Nishimura MI (2005) Simultaneous generation of CD8+ and CD4+ melanoma-reactive T cells by retroviral-mediated transfer of a single T-cell receptor. Cancer Res 65:1570–1576CrossRefPubMedGoogle Scholar
  13. 13.
    June CH, Maus MV, Plesa G, Johnson LA, Zhao Y, Levine BL, Grupp SA, Porter DL (2014) Engineered T cells for cancer therapy. Cancer Immunol Immunother 63:969–975CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Rosenberg SA, Restifo NP, Yang JC, Morgan RA, Dudley ME (2008) Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nat Rev Cancer 8:299–308CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Mehrotra S, Al-Khami AA, Klarquist J, Husain S, Naga O, Eby JM, Murali AK, Lyons GE, Li M, Spivey ND, Norell H, Martins da Palma T, Onicescu G, Diaz-Montero CM, Garrett-Mayer E, Cole DJ, Le Poole IC, Nishimura MI (2012) A coreceptor-independent transgenic human TCR mediates anti-tumor and anti-self immunity in mice. J Immunol 189:1627–1638CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Nishimura MI, Avichezer D, Custer MC, Lee CS, Chen C, Parkhurst MR, Diamond RA, Robbins PF, Schwartzentruber DJ, Rosenberg SA (1999) MHC class I-restricted recognition of a melanoma antigen by a human CD4+ tumor infiltrating lymphocyte. Cancer Res 59:6230–6238PubMedGoogle Scholar
  17. 17.
    Roszkowski JJ, Yu DC, Rubinstein MP, McKee MD, Cole DJ, Nishimura MI (2003) CD8-independent tumor cell recognition is a property of the T cell receptor and not the T cell. J Immunol 170:2582–2589CrossRefPubMedGoogle Scholar
  18. 18.
    Rosenberg SA, Restifo NP (2015) Adoptive cell transfer as personalized immunotherapy for human cancer. Science 348:62–68CrossRefPubMedGoogle Scholar
  19. 19.
    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 314:126–129CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Johnson LA, Morgan RA, Dudley ME, Cassard L, Yang JC, Hughes MS, Kammula US, Royal RE, Sherry RM, Wunderlich JR, Lee CC, 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 114:535–546CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    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 CC, 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 29:917–924CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Morgan RA, Chinnasamy N, Abate-Daga D, Gros A, Robbins PF, Zheng Z, Dudley ME, Feldman SA, Yang JC, Sherry RM, Phan GQ, Hughes MS, Kammula US, Miller AD, Hessman CJ, Stewart AA, Restifo NP, Quezado MM, Alimchandani M, Rosenberg AZ, Nath A, Wang T, Bielekova B, Wuest SC, Akula N, McMahon FJ, Wilde S, Mosetter B, Schendel DJ, Laurencot CM, Rosenberg SA (2013) Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy. J Immunother 36:133–151CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Parkhurst MR, Yang JC, Langan RC, Dudley ME, Nathan DA, 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 19:620–626CrossRefPubMedGoogle Scholar
  24. 24.
    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 23:2346–2357CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Ellebaek E, Iversen TZ, Junker N, Donia M, Engell-Noerregaard L, Met Ö, Hölmich LR, Andersen RS, Hadrup SR, Andersen MH, thor Straten P, Svane IM (2012) Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients. J Transl Med 10:169CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Andersen R, Donia M, Ellebaek E, Borch TH, Kongsted P, Iversen TZ, Hölmich LR, Hendel HW, Met Ö, 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 22:3734–3745CrossRefPubMedGoogle Scholar
  27. 27.
    Davis-Harrison RL, Armstrong KM, Baker BM (2005) Two different T cell receptors use different thermodynamic strategies to recognize the same peptide/MHC ligand. J Mol Biol 346:533–550CrossRefPubMedGoogle Scholar
  28. 28.
    Blevins SJ, Baker BM (2017) Using global analysis to extend the accuracy and precision of binding measurements with T cell receptors and their peptide/MHC ligands. Front Mol Biosci 4:2CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Huang J, Zarnitsyna VI, Liu B, Edwards LJ, Jiang N, Evavold BD, Zhu C (2010) The kinetics of two-dimensional TCR and pMHC interactions determine T-cell responsiveness. Nature 464:932–936CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Martinez RJ, Andargachew R, Martinez HA, Evavold BD (2016) Low-affinity CD4+ T cells are major responders in the primary immune response. Nat Commun 7:13848CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Dudley ME, Wunderlich JR, Yang JC, Hwu P, Schwartzentruber DJ, Topalian SL, Sherry RM, Marincola FM, Leitman SF, Seipp CA, Rogers-Freezer L, Morton KE, Nahvi A, Mavroukakis SA, White DE, Rosenberg SA (2002) A phase I study of nonmyeloablative chemotherapy and adoptive transfer of autologous tumor antigen-specific T lymphocytes in patients with metastatic melanoma. J Immunother 25:243–251CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Norell H, Zhang Y, McCracken J, Martins da Palma T, Lesher A, Liu Y, Roszkowski JJ, Temple A, Callender GG, Clay T, Orentas R, Guevara-Patiño J, Nishimura MI (2010) CD34-based enrichment of genetically engineered human T cells for clinical use results in dramatically enhanced tumor targeting. Cancer Immunol Immunother 59:851–862CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Ahmadi M, King JW, Xue SA, Voisine C, Holler A, Wright GP, Waxman J, Morris E, Stauss HJ (2011) CD3 limits the efficacy of TCR gene therapy in vivo. Blood 118:3528–3537CrossRefPubMedGoogle Scholar
  34. 34.
    Simms PE, Ellis TM (1996) Utility of flow cytometric detection of CD69 expression as a rapid method for determining poly- and oligoclonal lymphocyte activation. Clin Diagn Lab Immunol 3:301–304PubMedPubMedCentralGoogle Scholar
  35. 35.
    Cerdan C, Martin Y, Courcoul M, Brailly H, Mawas C, Birg F, Olive D (1992) Prolonged IL-2 receptor alpha/CD25 expression after T cell activation via the adhesion molecules CD2 and CD28. Demonstration of combined transcriptional and post-transcriptional regulation. J Immunol 149:2255–2261PubMedGoogle Scholar
  36. 36.
    Ahmadzadeh M, Johnson LA, Heemskerk B, Wunderlich JR, Dudley ME, White DE, Rosenberg SA (2009) Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood 114:1537–1544CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Gros A, Robbins PF, Yao X, Li YF, Turcotte S, Tran E, Wunderlich JR, Mixon A, Farid S, Dudley ME, Hanada K, Almeida JR, Darko S, Douek DC, Yang JC, Rosenberg SA (2014) PD-1 identifies the patient-specific CD8+ tumor-reactive repertoire infiltrating human tumors. J Clin Invest 124:2246–2259CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Inozume T, Hanada K, Wang QJ, Ahmadzadeh M, Wunderlich JR, Rosenberg SA, Yang JC (2010) Selection of CD8+PD-1+ lymphocytes in fresh human melanomas enriches for tumor-reactive T cells. J Immunother 33:956–964CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Fourcade J, Sun Z, Benallaoua M, Guillaume P, Luescher IF, Sander C, Kirkwood JM, Kuchroo V, Zarour HM (2010) Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen-specific CD8+ T cell dysfunction in melanoma patients. J Exp Med 207:2175–2186CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, Segal NH, Ariyan CE, Gordon RA, Reed K, Burke MM, Caldwell A, Kronenberg SA, Agunwamba BU, Zhang X, Lowy I, Inzunza HD, Feely W, Horak CE, Hong Q, Korman AJ, Wigginton JM, Gupta A, Sznol M (2013) Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med 369:122–133CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, Brahmer JR, Lawrence DP, Atkins MB, Powderly JD, Leming PD, Lipson EJ, Puzanov I, Smith DC, Taube JM, Wigginton JM, Kollia GD, Gupta A, Pardoll DM, Sosman JA, Hodi FS (2014) Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol 32:1020–1030CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Ribas A, Camacho LH, Lopez-Berestein G, Pavlov D, Bulanhagui CA, Millham R, Comin-Anduix B, Reuben JM, Seja E, Parker CA, Sharma A, Glaspy JA, Gomez-Navarro J (2005) Antitumor activity in melanoma and anti-self responses in a phase I trial with the anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody CP-675,206. J Clin Oncol 23:8968–8977CrossRefPubMedGoogle Scholar
  43. 43.
    Schadendorf D, Hodi FS, Robert C, Weber JS, Margolin K, Hamid O, Patt D, Chen TT, Berman DM, Wolchok JD (2015) Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma. J Clin Oncol 33:1889–1894CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Callahan MK, Wolchok JD, Allison JP (2010) Anti-CTLA-4 antibody therapy: immune monitoring during clinical development of a novel immunotherapy. Semin Oncol 37:473–484CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Yuan J, Ginsberg B, Page D, Li Y, Rasalan T, Gallardo HF, Xu Y, Adams S, Bhardwaj N, Busam K, Old LJ, Allison JP, Jungbluth A, Wolchok JD (2011) CTLA-4 blockade increases antigen-specific CD8(+) T cells in prevaccinated patients with melanoma: three cases. Cancer Immunol Immunother 60:1137–1146CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Kitano S, Tsuji T, Liu C, Hirschhorn-Cymerman D, Kyi C, Mu Z, Allison JP, Gnjatic S, Yuan JD, Wolchok JD (2013) Enhancement of tumor-reactive cytotoxic CD4+ T cell responses after ipilimumab treatment in four advanced melanoma patients. Cancer Immunol Res 1:235–244CrossRefPubMedGoogle Scholar
  47. 47.
    Baitsch L, Legat A, Barba L, Fuertes Marraco SA, Rivals JP, Baumgaertner P, Christiansen-Jucht C, Bouzourene H, Rimoldi D, Pircher H, Rufer N, Matter M, Michielin O, Speiser DE (2012) Extended co-expression of inhibitory receptors by human CD8 T-cells depending on differentiation, antigen-specificity and anatomical localization. PLoS ONE 7:e30852CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Viguier M, Lemaître F, Verola O, Cho MS, Gorochov G, Dubertret L, Bachelez H, Kourilsky P, Ferradini L (2004) Foxp3 expressing CD4+CD25(high) regulatory T cells are overrepresented in human metastatic melanoma lymph nodes and inhibit the function of infiltrating T cells. J Immunol 173:1444–1453CrossRefPubMedGoogle Scholar
  49. 49.
    Watts TH (2005) TNF/TNFR family members in costimulation of T cell responses. Annu Rev Immunol 23:23–68CrossRefPubMedGoogle Scholar
  50. 50.
    Croft M, So T, Duan W, Soroosh P (2009) The significance of OX40 and OX40L to T-cell biology and immune disease. Immunol Rev 229:173–191CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Vetto JT, Lum S, Morris A, Sicotte M, Davis J, Lemon M, Weinberg A (1997) Presence of the T-cell activation marker OX-40 on tumor infiltrating lymphocytes and draining lymph node cells from patients with melanoma and head and neck cancers. Am J Surg 174:258–265CrossRefPubMedGoogle Scholar
  52. 52.
    Weinberg AD, Rivera MM, Prell R, Morris A, Ramstad T, Vetto JT, Urba WJ, Alvord G, Bunce C, Shields J (2000) Engagement of the OX-40 receptor in vivo enhances antitumor immunity. J Immunol 164:2160–2169CrossRefPubMedGoogle Scholar
  53. 53.
    Ladányi A, Somlai B, Gilde K, Fejös Z, Gaudi I, Tímár J (2004) T-cell activation marker expression on tumor-infiltrating lymphocytes as prognostic factor in cutaneous malignant melanoma. Clin Cancer Res 10:521–530CrossRefPubMedGoogle Scholar
  54. 54.
    Sallusto F, Lanzavecchia A (2000) Understanding dendritic cell and T-lymphocyte traffic through the analysis of chemokine receptor expression. Immunol Rev 177:134–140CrossRefPubMedGoogle Scholar
  55. 55.
    Martinez RJ, Evavold BD (2015) Lower affinity T cells are critical components and active participants of the immune response. Front Immunol 6:468CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Coulie PG, Somville M, Lehmann F, Hainaut P, Brasseur F, Devos R, Boon T (1992) Precursor frequency analysis of human cytolytic T lymphocytes directed against autologous melanoma cells. Int J Cancer 50:289–297CrossRefPubMedGoogle Scholar
  57. 57.
    Tan MP, Gerry AB, Brewer JE, Melchiori L, Bridgeman JS, Bennett AD, Pumphrey NJ, Jakobsen BK, Price DA, Ladell K, Sewell AK (2015) T cell receptor binding affinity governs the functional profile of cancer-specific CD8+ T cells. Clin Exp Immunol 180:255–270CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Aleksic M, Liddy N, Molloy PE, Pumphrey N, Vuidepot A, Chang KM, Jakobsen BK (2012) Different affinity windows for virus and cancer-specific T-cell receptors: implications for therapeutic strategies. Eur J Immunol 42:3174–3179CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Baitsch L, Baumgaertner P, Devêvre E, Raghav SK, Legat A, Barba L, Wieckowski S, Bouzourene H, Deplancke B, Romero P, Rufer N, Speiser DE (2011) Exhaustion of tumor-specific CD8+ T cells in metastases from melanoma patients. J Clin Invest 121:2350–2360CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Chapuis AG, Thompson JA, Margolin KA, Rodmyre R, Lai IP, Dowdy K, Farrar EA, Bhatia S, Sabath DE, Cao J, Li Y, Yee C (2012) Transferred melanoma-specific CD8+ T cells persist, mediate tumor regression, and acquire central memory phenotype. Proc Natl Acad Sci USA 109:4592–4597CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Yee C, Thompson JA, Byrd D, Riddell SR, Roche P, Celis E, Greenberg PD (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 USA 99:16168–16173CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    McGranahan N, Furness AJ, Rosenthal R, Ramskov S, Lyngaa R, Saini SK, Jamal-Hanjani M, Wilson GA, Birkbak NJ, Hiley CT, Watkins TB, Shafi S, Murugaesu N, Mitter R, Akarca AU, Linares J, Marafioti T, Henry JY, Van Allen EM, Miao D, Schilling B, Schadendorf D, Garraway LA, Makarov V, Rizvi NA, Snyder A, Hellmann MD, Merghoub T, Wolchok JD, Shukla SA, Wu CJ, Peggs KS, Chan TA, Hadrup SR, Quezada SA, Swanton C (2016) Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science 351:1463–1469CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Lu YC, Yao X, Crystal JS, Li YF, El-Gamil M, Gross C, Davis L, Dudley ME, Yang JC, Samuels Y, Rosenberg SA, Robbins PF (2014) Efficient identification of mutated cancer antigens recognized by T cells associated with durable tumor regressions. Clin Cancer Res 20:3401–3410CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Campesato LF, Barroso-Sousa R, Jimenez L, Correa BR, Sabbaga J, Hoff PM, Reis LF, Galante PA, Camargo AA (2015) Comprehensive cancer-gene panels can be used to estimate mutational load and predict clinical benefit to PD-1 blockade in clinical practice. Oncotarget 6:34221–34227CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A, Walsh LA, Postow MA, Wong P, Ho TS, Hollmann TJ, Bruggeman C, Kannan K, Li Y, Elipenahli C, Liu C, Harbison CT, Wang L, Ribas A, Wolchok JD, Chan TA (2014) Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med 371:2189–2199CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Roszik J, Haydu LE, Hess KR, Oba J, Joon AY, Siroy AE, Karpinets TV, Stingo FC, Baladandayuthapani V, Tetzlaff MT, Wargo JA, Chen K, Forget MA, Haymaker CL, Chen JQ, Meric-Bernstam F, Eterovic AK, Shaw KR, Mills GB, Gershenwald JE, Radvanyi LG, Hwu P, Futreal PA, Gibbons DL, Lazar AJ, Bernatchez C, Davies MA, Woodman SE (2016) Novel algorithmic approach predicts tumor mutation load and correlates with immunotherapy clinical outcomes using a defined gene mutation set. BMC Med 14:168CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Rabinovich GA, Gabrilovich D, Sotomayor EM (2007) Immunosuppressive strategies that are mediated by tumor cells. Annu Rev Immunol 25:267–296CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Hodi FS, Butler M, Oble DA, Seiden MV, Haluska FG, Kruse A, Macrae S, Nelson M, Canning C, Lowy I, Korman A, Lautz D, Russell S, Jaklitsch MT, Ramaiya N, Chen TC, Neuberg D, Allison JP, Mihm MC, Dranoff G (2008) Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients. Proc Natl Acad Sci USA 105:3005–3010CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Quezada SA, Peggs KS, Curran MA, Allison JP (2006) CTLA4 blockade and GM-CSF combination immunotherapy alters the intratumor balance of effector and regulatory T cells. J Clin Invest 116:1935–1945CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Martens A, Wistuba-Hamprecht K, Geukes Foppen M, Yuan J, Postow MA, Wong P, Romano E, Khammari A, Dreno B, Capone M, Ascierto PA, Di Giacomo AM, Maio M, Schilling B, Sucker A, Schadendorf D, Hassel JC, Eigentler TK, Martus P, Wolchok JD, Blank C, Pawelec G, Garbe C, Weide B (2016) Baseline peripheral blood biomarkers associated with clinical outcome of advanced melanoma patients treated with ipilimumab. Clin Cancer Res 22:2908–2918CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Khong HT, Wang QJ, Rosenberg SA (2004) Identification of multiple antigens recognized by tumor-infiltrating lymphocytes from a single patient: tumor escape by antigen loss and loss of MHC expression. J Immunother 27:184–190CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Maeurer MJ, Gollin SM, Martin D, Swaney W, Bryant J, Castelli C, Robbins P, Parmiani G, Storkus WJ, Lotze MT (1996) Tumor escape from immune recognition: lethal recurrent melanoma in a patient associated with downregulation of the peptide transporter protein TAP-1 and loss of expression of the immunodominant MART-1/Melan-A antigen. J Clin Invest 98:1633–1641CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Rosenberg SA, Yang JC, Robbins PF, Wunderlich JR, Hwu P, Sherry RM, Schwartzentruber DJ, Topalian SL, Restifo NP, Filie A, Chang R, Dudley ME (2003) Cell transfer therapy for cancer: lessons from sequential treatments of a patient with metastatic melanoma. J Immunother 26:385–393CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Villadangos JA (2016) Antigen-specific impairment of adoptive T-cell therapy against cancer: players, mechanisms, solutions and a hypothesis. Immunol Rev 272:169–182CrossRefPubMedGoogle Scholar
  75. 75.
    Huang AC, Postow MA, Orlowski RJ, Mick R, Bengsch B, Manne S, Xu W, Harmon S, Giles JR, Wenz B, Adamow M, Kuk D, Panageas KS, Carrera C, Wong P, Quagliarello F, Wubbenhorst B, D’Andrea K, Pauken KE, Herati RS, Staupe RP, Schenkel JM, McGettigan S, Kothari S, George SM, Vonderheide RH, Amaravadi RK, Karakousis GC, Schuchter LM, Xu X, Nathanson KL, Wolchok JD, Gangadhar TC, Wherry EJ (2017) T-cell invigoration to tumour burden ratio associated with anti-PD-1 response. Nature 545:60–65CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Tamson Moore
    • 1
  • Courtney Regan Wagner
    • 2
  • Gina M. Scurti
    • 1
  • Kelli A. Hutchens
    • 3
    • 4
  • Constantine Godellas
    • 1
  • Ann Lau Clark
    • 2
  • Elizabeth Motunrayo Kolawole
    • 5
  • Lance M. Hellman
    • 6
  • Nishant K. Singh
    • 6
  • Fernando A. Huyke
    • 6
  • Siao-Yi Wang
    • 1
  • Kelly M. Calabrese
    • 1
    • 7
  • Heather D. Embree
    • 8
  • Rimas Orentas
    • 8
  • Keisuke Shirai
    • 9
    • 10
  • Emilia Dellacecca
    • 3
    • 11
  • Elizabeth Garrett-Mayer
    • 9
  • Mingli Li
    • 9
    • 12
  • Jonathan M. Eby
    • 3
    • 11
  • Patrick J. Stiff
    • 2
  • Brian D. Evavold
    • 5
  • Brian M. Baker
    • 6
  • I. Caroline Le Poole
    • 3
    • 11
    • 13
  • Boro Dropulic
    • 8
  • Joseph I. Clark
    • 2
  • Michael I. Nishimura
    • 1
  1. 1.Department of SurgeryLoyola University ChicagoMaywoodUSA
  2. 2.Department of MedicineLoyola University ChicagoMaywoodUSA
  3. 3.Department of PathologyLoyola University ChicagoMaywoodUSA
  4. 4.Forefront DermatologyManitowocUSA
  5. 5.O. Wayne Rollins Research CenterEmory UniversityAtlantaUSA
  6. 6.Department of Chemistry & Biochemistry and the Harper Cancer Research InstituteUniversity of Notre DameNotre DameUSA
  7. 7.AbbvieNorth ChicagoUSA
  8. 8.Lentigen Technology Inc, A Miltenyi Biotec CompanyGaithersburgUSA
  9. 9.Hollings Cancer CenterMedical University of South CarolinaCharlestonUSA
  10. 10.Dartmouth-Hitchcock, Norris Cotton Cancer CenterLebanonUSA
  11. 11.Department of Microbiology, and ImmunologyLoyola University ChicagoMaywoodUSA
  12. 12.Bluebird BiologyCambridgeUSA
  13. 13.Lurie Comprehensive Cancer Center, Department of DermatologyNorthwestern University at ChicagoChicagoUSA

Personalised recommendations