Development of PD-1 blockade peptide-cell conjugates to enhance cellular therapies for T-cell acute lymphoblastic leukemia

Med Oncol. 2023 Dec 11;41(1):14. doi: 10.1007/s12032-023-02235-y.

Abstract

Blockade of the interaction of the immune checkpoint receptor programmed cell death protein (PD)-1 and its ligand PD-L1 has been found to be a promising cancer treatment. Our previous studies identified that nABPD1 competed with PD-L1 to bind PD-1. The aim of this study was to evaluate the efficacy and safety of anti-tumor immunotherapy of ICIK cells conjugated with peptides in vivo and in vitro. Here, we synthesized the nABPD1 derivatives SBP1 and SBP2 and showed that their binding efficiency to PD-1-positive improving cytokine-induced killer (ICIK) cells was 98 and 82%, respectively. The cytotoxicity of ICIK cells to T-cell acute lymphoblastic leukemia (T-ALL) cells was increased by conjugating with SBP1 or SBP2, which was 2 times higher than that of ICIK cells alone. Furthermore, mice experiments showed that the fluorescence intensity of leukemia cells in T-ALL xenograft models was reduced by more than 95%, indicating that the peptides enhanced the therapeutic effect in vivo, while morphological evaluations showed that the peptides had no toxicity to important organs. Therefore, peptide-cell conjugates (PCCs) may be a novel method to improve the efficacy of cancer immunotherapy by blocking PD-1 in T-ALL patients.

Keywords: ICIK; Immunotherapy; PCCs; PD-1 binding peptide; T-ALL.

MeSH terms

  • Animals
  • B7-H1 Antigen*
  • Humans
  • Immunotherapy / methods
  • Mice
  • Peptides
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma* / therapy
  • Programmed Cell Death 1 Receptor
  • T-Lymphocytes / metabolism

Substances

  • B7-H1 Antigen
  • Programmed Cell Death 1 Receptor
  • Peptides