title: Multifunctional T-cell analyses to study response and progression in adoptive cell transfer immunotherapy.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: NanoSystems Biology Cancer Center, Division of Physics, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Ma
authors.forename: Ann F
authors.initials: AF
authors.lastname: Cheung
authors.forename: Thinle
authors.initials: T
authors.lastname: Chodon
authors.forename: Richard C
authors.initials: RC
authors.lastname: Koya
authors.forename: Zhongqi
authors.initials: Z
authors.lastname: Wu
authors.forename: Charles
authors.initials: C
authors.lastname: Ng
authors.forename: Earl
authors.initials: E
authors.lastname: Avramis
authors.forename: Alistair J
authors.initials: AJ
authors.lastname: Cochran
authors.forename: Owen N
authors.initials: ON
authors.lastname: Witte
authors.forename: David
authors.initials: D
authors.lastname: Baltimore
authors.forename: Bartosz
authors.initials: B
authors.lastname: Chmielowski
authors.forename: James S
authors.initials: JS
authors.lastname: Economou
authors.forename: Begonya
authors.initials: B
authors.lastname: Comin-Anduix
authors.forename: Antoni
authors.initials: A
authors.lastname: Ribas
authors.forename: James R
authors.initials: JR
authors.lastname: Heath
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D058965:MART-1 Antigen / Q000276:immunology*; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D058965:MART-1 Antigen; D011948:Receptors, Antigen, T-Cell