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Exploiting the curative potential of adoptive T‐cell therapy for cancer
Author(s) -
Hinrichs Christian S.,
Rosenberg Steven A.
Publication year - 2014
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/imr.12132
Subject(s) - chimeric antigen receptor , adoptive cell transfer , melanoma , cancer research , immunology , cd19 , cancer , antigen , cell therapy , immunotherapy , tumor infiltrating lymphocytes , medicine , t cell , biology , immune system , cell , genetics
Summary Adoptive T‐cell therapy ( ACT ) is a potent and flexible cancer treatment modality that can induce complete, durable regression of certain human malignancies. Long‐term follow‐up of patients receiving tumor‐infiltrating lymphocytes ( TIL s) for metastatic melanoma reveals a substantial subset that experienced complete, lasting tumor regression – and may be cured. Increasing evidence points to mutated gene products as the primary immunological targets of TIL s from melanomas. Recent technological advances permit rapid identification of the neoepitopes resulting from these somatic gene mutations and of T cells with reactivity against these targets. Isolation and adoptive transfer of these T cells may improve TIL therapy for melanoma and permit its broader application to non‐melanoma tumors. Extension of ACT to other malignancies may also be possible through antigen receptor gene engineering. Tumor regression has been observed following transfer of T cells engineered to express chimeric antigen receptors against CD 19 in B‐cell malignancies or a T‐cell receptor against NY ‐ ESO ‐1 in synovial cell sarcoma and melanoma. Herein, we review recent clinical trials of TIL s and antigen receptor gene therapy for advanced cancers. We discuss lessons from this experience and consider how they might be applied to realize the full curative potential of ACT .