Aminobisphosphonate-activated gammadelta T cells in immunotherapy of cancer: doubts no more

Expert Opin Biol Ther. 2008 Jul;8(7):875-83. doi: 10.1517/14712598.8.7.875.

Abstract

Background: Activated V gamma 9 V delta 2 T cells are able to kill most tumour cells because of recognition by T cell receptor and natural killer receptors.

Objective: We discuss the possibility that the intentional activation of gammadelta T cells in vivo by aminobisphosphonates may represent a promising target for the design of novel and highly innovative immunotherapy in cancer patients.

Methods: The antitumoral effects of gammadelta T cells both in vitro and in vivo have been demonstrated suggesting a new therapeutic approach for translation into the clinical setting.

Results/conclusion: V gamma 9 V delta 2 T lymphocytes represent a particularly interesting target for immunotherapeutic protocols based on N-aminobisphosphonate administration and several Phase I-II trials are ongoing investigating the activity of zoledronic acid plus IL-2 in solid tumours.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Clinical Trials as Topic
  • Diphosphonates / pharmacology*
  • Humans
  • Immune System
  • Immunologic Memory
  • Immunotherapy / methods*
  • Interleukin-2 / chemistry
  • Interleukin-2 / therapeutic use
  • Killer Cells, Natural / cytology*
  • Models, Biological
  • Neoplasms / metabolism*
  • Neoplasms / therapy*
  • Receptors, Antigen, T-Cell / metabolism*
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*
  • T-Lymphocyte Subsets / cytology*

Substances

  • Antineoplastic Agents
  • Diphosphonates
  • Interleukin-2
  • Receptors, Antigen, T-Cell
  • Receptors, Antigen, T-Cell, gamma-delta