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


Authors: Moore, T; Wagner, C. R.; Scurti, G. M.; Hutchens, K. A.; Godellas, C; Clark, A. L.; Kolawole, E. M.; Hellman, L. M.; Singh, N. K.; Huyke, F. A.; Wang, S. Y.; Calabrese, K. M.; Embree, H. D.; Orentas, R; Shirai, K; Dellacecca, E; Garrett-Mayer, E; Li, M; Eby, J. M.; Stiff, P. J.; Evavold, B. D.; Baker, B. M.; Le Poole, I. C.; Dropulic, B; Clark, J. I.; Nishimura, M. I.
Article Title: Clinical and immunologic evaluation of three metastatic melanoma patients treated with autologous melanoma-reactive TCR-transduced T cells
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: Immunotherapy; Adoptive Transfer; vitiligo; Clinical trial; Metastatic melanoma; Transduced T cells
Journal Title: Cancer immunology, immunotherapy : CII
Volume: 67
Issue: 2
ISSN: 1432-0851; 0340-7004
Publisher: Unknown  
Journal Place: Germany
Date Published: 2018
Start Page: 311
End Page: 325
Language: eng
DOI/URL:
Notes: LR: 20180314; GR: R43 CA126461/National Institutes of Health/United States; GR: P01 CA154778/National Institutes of Health/United States; GR: R01 CA104947-S1/National Institutes of Health/United States; GR: R44 CA126461/National Institutes of Health/United States; GR: R01 AI129543-01/National Institutes of Health/United States; GR: R01 CA104947/National Institutes of Health/United States; GR: R01 AI096879/National Institutes of Health/United States; GR: R01 CA90873/National Institutes of Health/United States; GR: R01 AI129543/AI/NIAID NIH HHS/United States; JID: 8605732; EIN: Cancer Immunol Immunother. 2017 Dec 20;:. PMID: 29264697; OTO: NOTNLM; 2017/03/04 00:00 [received]; 2017/10/03 00:00 [accepted]; 2017/10/21 06:00 [pubmed]; 2017/10/21 06:00 [medline]; 2017/10/21 06:00 [entrez]; ppublish