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

Cancer Discov
Publication Year: 
Chao Ma
Ann F Cheung
Thinle Chodon
Richard C Koya
Zhongqi Wu
Charles Ng
Earl Avramis
Alistair J Cochran
Owen N Witte
David Baltimore
Bartosz Chmielowski
James S Economou
Begonya Comin-Anduix
Antoni Ribas
James R Heath
PubMed link: 
Public Summary: 
Scientific 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.