Delayed IL-21 treatment preferentially expands peptide-specific CD8+ T cells by reducing bystander activation of T cells

Immunotherapy. 2019 Apr;11(6):497-513. doi: 10.2217/imt-2018-0095. Epub 2019 Feb 14.

Abstract

Aim: We previously reported a simple and practical procedure to generate peptide-specific CD8+ T cells using peptide and IL-2, which is applied to produce human telomerase reverse transcriptase (hTERT)-specific CD8+ T cells for clinical use. We have modified the procedure to enhance the amplification of peptide-specific CD8+ T cells adding IL-21.

Materials & methods: Using human leukocyte antigen (HLA)-A*0201-restricted cytomegalovirus/pp65-specific CD8+ T cells of healthy volunteers, we optimized the culture conditions by adjusting the dose and timing of IL-21 treatment.

Results & conclusion: By adding IL-21, we accelerated the expansion rate of cytomegalovirus/pp65-specific CD8+ T cells by reducing bystander activation of T cells. We expect that the procedure including IL-21 would improve the production rate of hTERT- and Wilms tumor 1 (WT1)-specific CD8+ T cells for clinical trials.

Keywords: 4-1BB; CD137; CD8 T cells; IL-21; immunotherapy; tumor-associated antigen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / immunology
  • Bystander Effect
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Cells, Cultured
  • HLA-A2 Antigen / metabolism
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Interleukins / metabolism*
  • Lymphocyte Activation
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Peptides / immunology
  • Peptides / metabolism
  • Protein Binding
  • T-Cell Antigen Receptor Specificity
  • Viral Matrix Proteins / immunology
  • Viral Matrix Proteins / metabolism

Substances

  • Antigens, Neoplasm
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • Interleukins
  • Peptides
  • Viral Matrix Proteins
  • cytomegalovirus matrix protein 65kDa
  • interleukin-21