Multifunctional T-cell Analyses to Study Response and Progression in Adoptive Cell Transfer Immunotherapy

1NanoSystems Biology Cancer Center, 2Division of Chemistry and Chemical Engineering, 3Division of Physics, Mathematics, and Astronomy, and 4Division of Biology, California Institute of Technology, Pasadena
Cancer Discovery (Impact Factor: 19.45). 03/2013; 3(4). DOI: 10.1158/2159-8290.CD-12-0383
Source: PubMed


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.

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.

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    • "Ma's team assayed a panel of 12 secreted proteins and found a large (albeit not statistically random) range of functional phenotypes within a tightly defined T-cell phenotype [4]. A follow-up kinetic study [5] helped define some of this functional diversity (Figure 2). The authors [5] studied three melanoma cancer patients participating in the same ACT trial and combined 19-plex SCBC functional (secreted) protein assays with 10-color FACS to measure the functional evolution of specific T-cell phenotypes at 5 to 10 time points over a 90-day trial (Figure 2a). "
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    Preview · Article · Apr 2013 · Cancer Discovery
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