At the bedside: adoptive cell therapy for melanoma-clinical development

J Leukoc Biol. 2014 Jun;95(6):875-82. doi: 10.1189/jlb.0513293. Epub 2014 Apr 14.

Abstract

Adoptive cell therapy for melanoma, particularly using TIL, consists of a complex and difficult set of procedures, although it has a strong preclinical background and justification and has been pursued clinically by one small group of investigators over the last 20 years. More recent developments and a better understanding of the molecular basis of the anti-tumor immune response have led to the conduct of clinical trials that use lymphoid depletion with chemotherapy and/or TBI to exploit the favorable immune milieu of homeostatic lymphoid reconstitution during transfer of effector T cells. Improved ways of propagating T cells ex vivo have also simplified and shortened the cell-growth process. Current TIL trials have now been expanded beyond the initial center where it was developed, reproducing excellent objective response rates of 40-50% in previously treated melanoma patients and more importantly, demonstrating that a significant proportion of patients will be alive and free of disease 3-5 years after treatment, raising the possibility that those patients may be cured of their disease. Newer methods for growing the infiltrating T cells using immune-checkpoint antibodies or other agents to condition the tumor before harvest and improved technology to simplify the complex and often cumbersome cell-growth process suggest that this technology may be able to be disseminated to a wide selection of cancer centers and may be a candidate for testing in a randomized Phase III trial to show definitively its benefit in patients with metastatic melanoma. In the accompanying review, the preclinical work that supports the idea of adoptive cell therapy with TIL and expands the concept in promising new ways will be explored.

Keywords: IL-2; T cell; T cell receptor; immunotherapy; lymphoid depletion.

Publication types

  • Review

MeSH terms

  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / immunology
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Interleukin-2 / pharmacology
  • Killer Cells, Lymphokine-Activated / immunology
  • Killer Cells, Natural / immunology
  • Lymphocyte Depletion
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Melanoma / immunology
  • Melanoma / therapy*
  • Receptors, Antigen, T-Cell / genetics

Substances

  • Cancer Vaccines
  • Interleukin-2
  • Receptors, Antigen, T-Cell