Characteristics of Human Peripheral Blood γδ T Cells Expanded With Zoledronate

Anticancer Res. 2021 Dec;41(12):6031-6038. doi: 10.21873/anticanres.15422.

Abstract

Background/aim: This study aimed to investigate the characteristics of human peripheral blood γδ T cells, which were expanded ex vivo in the presence of zoledronate (ZOL).

Materials and methods: Human peripheral blood cells were cultured with IL-2 and IL-15 in the presence or absence of ZOL, which was added as a phospho-antigen, and their phenotypes were assessed by flow cytometry. Expanded γδ T cells were transduced with CD19 CAR vector, and the cytotoxicity was evaluated in vitro and in vivo by flow cytometry.

Results: Ex vivo expansion did not hamper the expression of activating receptors. Interestingly, ZOL promoted the expression of CD226 (DNAM-1), TRAIL, and FAS-L in the Vδ1 subset of γδ T cells. Expanded γδ T cells containing CD19 CAR+ γδ T cells removed B cell lymphoma cells effectively in vivo.

Conclusion: γδ T cells could be a promising immunotherapeutic for cancer.

Keywords: chimeric antigen receptor; immunotherapy; γδ T cells.

MeSH terms

  • Animals
  • Antigens, CD19 / immunology
  • Antigens, Neoplasm / immunology
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cells, Cultured
  • Humans
  • Immunotherapy, Adoptive
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Mice
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / therapy
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*
  • Receptors, Chimeric Antigen
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / drug effects*
  • T-Lymphocyte Subsets / metabolism*
  • Zoledronic Acid / pharmacology*

Substances

  • Antigens, CD19
  • Antigens, Neoplasm
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Chimeric Antigen
  • Zoledronic Acid