Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 2/2018

01-02-2018 | Original Article

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

Authors: 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

Published in: Cancer Immunology, Immunotherapy | Issue 2/2018

Login to get access

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.
Appendix
Available only for authorised users
Literature
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.
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–E386CrossRefPubMed
3.
4.
5.
Callahan MK, Postow MA, Wolchok JD (2014) CTLA-4 and PD-1 pathway blockade: combinations in the clinic. Front Oncol 4:385PubMed
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 54:139–148CrossRefPubMed
7.
Teixidó C, González-Cao M, Karachaliou N, Rosell R (2015) Predictive factors for immunotherapy in melanoma. Ann Transl Med 3:208PubMedPubMedCentral
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 515:568–571CrossRefPubMedPubMedCentral
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 126:3447–3452CrossRefPubMedPubMedCentral
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 6:254ra128CrossRefPubMed
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 6:238ra270CrossRef
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 65:1570–1576CrossRefPubMed
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 63:969–975CrossRefPubMedPubMedCentral
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 8:299–308CrossRefPubMedPubMedCentral
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 189:1627–1638CrossRefPubMedPubMedCentral
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 59:6230–6238PubMed
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 170:2582–2589CrossRefPubMed
18.
Rosenberg SA, Restifo NP (2015) Adoptive cell transfer as personalized immunotherapy for human cancer. Science 348:62–68CrossRefPubMed
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 314:126–129CrossRefPubMedPubMedCentral
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 114:535–546CrossRefPubMedPubMedCentral
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 29:917–924CrossRefPubMedPubMedCentral
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 36:133–151CrossRefPubMedPubMedCentral
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 19:620–626CrossRefPubMed
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 23:2346–2357CrossRefPubMedPubMedCentral
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 10:169CrossRefPubMedPubMedCentral
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 22:3734–3745CrossRefPubMed
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 346:533–550CrossRefPubMed
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 4:2CrossRefPubMedPubMedCentral
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 464:932–936CrossRefPubMedPubMedCentral
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 7:13848CrossRefPubMedPubMedCentral
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 25:243–251CrossRefPubMedPubMedCentral
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 59:851–862CrossRefPubMedPubMedCentral
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 118:3528–3537CrossRefPubMed
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 3:301–304PubMedPubMedCentral
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 149:2255–2261PubMed
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 114:1537–1544CrossRefPubMedPubMedCentral
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 124:2246–2259CrossRefPubMedPubMedCentral
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 33:956–964CrossRefPubMedPubMedCentral
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 207:2175–2186CrossRefPubMedPubMedCentral
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 369:122–133CrossRefPubMedPubMedCentral
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 32:1020–1030CrossRefPubMedPubMedCentral
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 23:8968–8977CrossRefPubMed
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 33:1889–1894CrossRefPubMedPubMedCentral
44.
Callahan MK, Wolchok JD, Allison JP (2010) Anti-CTLA-4 antibody therapy: immune monitoring during clinical development of a novel immunotherapy. Semin Oncol 37:473–484CrossRefPubMedPubMedCentral
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 60:1137–1146CrossRefPubMedPubMedCentral
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 1:235–244CrossRefPubMed
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:e30852CrossRefPubMedPubMedCentral
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 173:1444–1453CrossRefPubMed
49.
Watts TH (2005) TNF/TNFR family members in costimulation of T cell responses. Annu Rev Immunol 23:23–68CrossRefPubMed
50.
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 174:258–265CrossRefPubMed
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 164:2160–2169CrossRefPubMed
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 10:521–530CrossRefPubMed
54.
Sallusto F, Lanzavecchia A (2000) Understanding dendritic cell and T-lymphocyte traffic through the analysis of chemokine receptor expression. Immunol Rev 177:134–140CrossRefPubMed
55.
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 50:289–297CrossRefPubMed
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 180:255–270CrossRefPubMedPubMedCentral
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 42:3174–3179CrossRefPubMedPubMedCentral
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 121:2350–2360CrossRefPubMedPubMedCentral
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 109:4592–4597CrossRefPubMedPubMedCentral
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 99:16168–16173CrossRefPubMedPubMedCentral
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 351:1463–1469CrossRefPubMedPubMedCentral
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 20:3401–3410CrossRefPubMedPubMedCentral
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 6:34221–34227CrossRefPubMedPubMedCentral
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 371:2189–2199CrossRefPubMedPubMedCentral
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 14:168CrossRefPubMedPubMedCentral
67.
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 105:3005–3010CrossRefPubMedPubMedCentral
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 116:1935–1945CrossRefPubMedPubMedCentral
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 22:2908–2918CrossRefPubMedPubMedCentral
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 27:184–190CrossRefPubMedPubMedCentral
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 98:1633–1641CrossRefPubMedPubMedCentral
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 26:385–393CrossRefPubMedPubMedCentral
74.
Villadangos JA (2016) Antigen-specific impairment of adoptive T-cell therapy against cancer: players, mechanisms, solutions and a hypothesis. Immunol Rev 272:169–182CrossRefPubMed
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 545:60–65CrossRefPubMedPubMedCentral
Metadata
Title
Clinical and immunologic evaluation of three metastatic melanoma patients treated with autologous melanoma-reactive TCR-transduced T cells
Authors
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
Publication date
01-02-2018
Publisher
Springer Berlin Heidelberg
Published in
Cancer Immunology, Immunotherapy / Issue 2/2018
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-017-2073-0

Other articles of this Issue 2/2018

Cancer Immunology, Immunotherapy 2/2018 Go to the issue

Original Article

A phase I vaccination study with dendritic cells loaded with NY-ESO-1 and α-galactosylceramide: induction of polyfunctional T cells in high-risk melanoma patients

Original Article

Cross-talk between TNF-α and IFN-γ signaling in induction of B7-H1 expression in hepatocellular carcinoma cells

Original Article

NY-ESO-1- and survivin-specific T-cell responses in the peripheral blood from patients with glioma

Original Article

Characterization of arthralgia induced by PD-1 antibody treatment in patients with metastasized cutaneous malignancies

Correction

Correction to: Characterization of the first fully human anti-TEM1 scFv in models of solid tumor imaging and immunotoxin-based therapy

Original Article

Absolute lymphocyte counts at end of induction correlate with distinct immune cell compartments in pediatric B cell precursor acute lymphoblastic leukemia
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits