Multifunctional T-cell analyses to study response and progression in adoptive cell transfer immunotherapy

C Ma, AF Cheung, T Chodon, RC Koya, Z Wu, C Ng… - Cancer discovery, 2013 - AACR
C Ma, AF Cheung, T Chodon, RC Koya, Z Wu, C Ng, E Avramis, AJ Cochran, ON Witte…
Cancer discovery, 2013AACR
Adoptive cell transfer (ACT) of genetically engineered T cells expressing cancer-specific T-
cell receptors (TCR) is a promising cancer treatment. Here, we investigate the in vivo
functional activity and dynamics of the transferred cells by analyzing samples from 3
representative patients with melanoma enrolled in a clinical trial of ACT with TCR transgenic
T cells targeted against the melanosomal antigen MART-1. The analyses included
evaluating 19 secreted proteins from individual cells from phenotypically defined T-cell …
Abstract
Adoptive cell transfer (ACT) of genetically engineered T cells expressing cancer-specific T-cell receptors (TCR) is a promising cancer treatment. Here, we investigate the in vivo functional activity and dynamics of the transferred cells by analyzing samples from 3 representative patients with melanoma enrolled in a clinical trial of ACT with TCR transgenic T cells targeted against the melanosomal antigen MART-1. The analyses included evaluating 19 secreted proteins from individual cells from phenotypically defined T-cell subpopulations, as well as the enumeration of T cells with TCR antigen specificity for 36 melanoma antigens. These analyses revealed the coordinated functional dynamics of the adoptively transferred, as well as endogenous, T cells, and the importance of highly functional T cells in dominating the antitumor immune response. This study highlights the need to develop approaches to maintaining antitumor T-cell functionality with the aim of increasing the long-term efficacy of TCR-engineered ACT immunotherapy.
Significance: A longitudinal functional study of adoptively transferred TCR–engineered lymphocytes yielded revealing snapshots for understanding the changes of antitumor responses over time in ACT immunotherapy of patients with advanced melanoma. Cancer Discov; 3(4); 418–29. ©2013 AACR.
See related commentary by Speiser, p. 379
This article is highlighted in the In This Issue feature, p. 363
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