Peptide-HLA-based immunotherapeutics platforms for direct modulation of antigen-specific T cells

Sci Rep. 2021 Sep 28;11(1):19220. doi: 10.1038/s41598-021-98716-z.

Abstract

Targeted pharmacologic activation of antigen-specific (AgS) T cells may bypass limitations inherent in current T cell-based cancer therapies. We describe two immunotherapeutics platforms for selective delivery of costimulatory ligands and peptide-HLA (pHLA) to AgS T cells. We engineered and deployed on these platforms an affinity-attenuated variant of interleukin-2, which selectively expands oligoclonal and polyfunctional AgS T cells in vitro and synergizes with CD80 signals for superior proliferation versus peptide stimulation.

MeSH terms

  • Animals
  • B7-1 Antigen / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • HLA-A Antigens / genetics
  • HLA-A Antigens / immunology
  • Humans
  • Immunotherapy / methods*
  • Lymphocyte Activation
  • Mice
  • Mice, Transgenic
  • Mutation
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Peptides / genetics
  • Peptides / immunology
  • Primary Cell Culture
  • Protein Engineering
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology*

Substances

  • B7-1 Antigen
  • HLA-A Antigens
  • Peptides
  • Recombinant Fusion Proteins