Exploiting the curative potential of adoptive T-cell therapy for cancer

Christian S. Hinrichs, Steven A. Rosenberg

Research output: Contribution to journalArticle

Abstract

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 (TILs) 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 TILs 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 CD19 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 TILs 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.

Original languageEnglish (US)
Pages (from-to)56-71
Number of pages16
JournalImmunological Reviews
Volume257
Issue number1
DOIs
StatePublished - Jan 2014
Externally publishedYes

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Cell- and Tissue-Based Therapy
T-Lymphocytes
Tumor-Infiltrating Lymphocytes
Antigen Receptors
Melanoma
Neoplasms
Genes
Synovial Sarcoma
Adoptive Transfer
T-Cell Antigen Receptor
Genetic Therapy
B-Lymphocytes
Clinical Trials
Mutation
Therapeutics

Keywords

  • Antigens
  • Cancer
  • Gene therapy
  • Immunotherapies
  • T cells
  • Tumor immunity

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Exploiting the curative potential of adoptive T-cell therapy for cancer. / Hinrichs, Christian S.; Rosenberg, Steven A.

In: Immunological Reviews, Vol. 257, No. 1, 01.2014, p. 56-71.

Research output: Contribution to journalArticle

Hinrichs, Christian S. ; Rosenberg, Steven A. / Exploiting the curative potential of adoptive T-cell therapy for cancer. In: Immunological Reviews. 2014 ; Vol. 257, No. 1. pp. 56-71.
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