Anti-γδ TCR antibody-expanded γδ T cells: a better choice for the adoptive immunotherapy of lymphoid malignancies

Cell Mol Immunol. 2012 Jan;9(1):34-44. doi: 10.1038/cmi.2011.16. Epub 2011 Jun 13.

Abstract

Cell-based immunotherapy for lymphoid malignancies has gained increasing attention as patients develop resistance to conventional treatments. γδ T cells, which have major histocompatibility complex (MHC)-unrestricted lytic activity, have become a promising candidate population for adoptive cell transfer therapy. We previously established a stable condition for expanding γδ T cells by using anti-γδ T-cell receptor (TCR) antibody. In this study, we found that adoptive transfer of the expanded γδ T cells to Daudi lymphoma-bearing nude mice significantly prolonged the survival time of the mice and improved their living status. We further investigated the characteristics of these antibody-expanded γδ T cells compared to the more commonly used phosphoantigen-expanded γδ T cells and evaluated the feasibility of employing them in the treatment of lymphoid malignancies. Slow but sustained proliferation of human peripheral blood γδ T cells was observed upon stimulation with anti-γδ TCR antibody. Compared to phosphoantigen-stimulated γδ T cells, the antibody-expanded cells manifested similar functional phenotypes and cytotoxic activity towards lymphoma cell lines. It is noteworthy that the anti-γδ TCR antibody could expand both the Vδ1 and Vδ2 subsets of γδ T cells. The in vitro-expanded Vδ1 T cells displayed comparable tumour cell-killing activity to Vδ2 T cells. Importantly, owing to higher C-C chemokine receptor 4 (CCR4) and CCR8 expression, the Vδ1 T cells were more prone to infiltrate CCL17- or CCL22-expressing lymphomas than the Vδ2 T cells. Characterizing the peripheral blood γδ T cells from lymphoma patients further confirmed that the anti-γδ TCR antibody-expanded γδ T cells could be a more efficacious choice for the treatment of lymphoid malignancies than phosphoantigen-expanded γδ T cells.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Antibodies / immunology
  • Antibodies / pharmacology*
  • Chemokine CCL17 / immunology
  • Chemokine CCL22 / immunology
  • Female
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Jurkat Cells
  • K562 Cells
  • Lymphoma / immunology
  • Lymphoma / therapy*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Neoplasm Transplantation
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Receptors, CCR4 / immunology
  • Receptors, CCR8 / immunology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / transplantation*
  • Transplantation, Autologous
  • Transplantation, Heterologous

Substances

  • Antibodies
  • CCL17 protein, human
  • CCL22 protein, human
  • CCR4 protein, human
  • CCR8 protein, human
  • Chemokine CCL17
  • Chemokine CCL22
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, CCR4
  • Receptors, CCR8