Antigen-specific CTLs: to produce autologous cells product for adoptive cellular therapy

Int J Infect Dis. 2017 Jun:59:37-43. doi: 10.1016/j.ijid.2017.03.015. Epub 2017 Mar 22.

Abstract

As antiretroviral therapy provides long term viral suppression but no cure, alternative therapies such as adoptive cellular therapy have thus been investigated in the anti-AIDS field.

Objective: This study sought to establish a HLA-A02 specific CTL cell culture method with comparison of the effects of different cytokines used in CTL cultivation to decide the best cultivation environment. In order to produce CTLs with targeted HLA-A02 restricted antigen specificity for adoptive cellular therapy, we evaluated autologous PBMC cultivation in different cytokine environment to select a better expansion condition to produce qualified CTL production.

Methods: We co-cultivated PBMC and peptides of these patients with HLA-A02 allele with different cytokines. After cultivation, multiple parameters were tested.

Results: 1) Cytokines IL-2 alone can effectively amplify HLA-A02 specific CTL cells, and the count of CTLs was >85% all through the process. 2) The HLA-A02 specific cells at the end of the cultivation were mainly CD3+CD8+ cells. 3) The interferon stimulation test had shown that the expanded CTLs secreted more IFN-γ than before cultivation (0.9% -11.70%).

Conclusion: This model of CTL cultivation is successful in redirecting the specificity of antigen recognition and safely for HLA-A02+ patients cell adoptive therapy.

Keywords: CTL; HLA-A02; cell adoptive immunotherapy.

MeSH terms

  • Adult
  • Alleles
  • Cells, Cultured
  • Cytokines / immunology
  • Female
  • HLA-A2 Antigen / immunology
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Leukocytes, Mononuclear / immunology
  • Male
  • Middle Aged
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Cytokines
  • HLA-A2 Antigen