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Cancer Discov. 2013 Apr;3(4):418-29. doi: 10.1158/2159-8290.CD-12-0383. Epub 2013 Mar 21.

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

Author information

1
NanoSystems Biology Cancer Center, Division of Physics, California Institute of Technology, Pasadena, CA 91125, USA.

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00910650.

PMID:
23519018
PMCID:
PMC3716460
DOI:
10.1158/2159-8290.CD-12-0383
[Indexed for MEDLINE]
Free PMC Article
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