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

• Published in: Medical oncology (Northwood, London, England) Vol. 41; no. 1; p. 14
• Main Authors: Wang, Quanxiao, Huang, Hongxing, Liang, Peisheng, Wang, Lili, Zheng, Junheng, Zhang, Yan, Wang, Hua
• Format: Journal Article
• Language: English
• Published: New York Springer US 11.12.2023; Springer Nature B.V
• Subjects: Hematology; Immunotherapy; Internal Medicine; Leukemia; Medicine; Medicine & Public Health; Oncology; Original Paper; Pathology; Peptides; PD-1 binding peptide; T-ALL; PCCs; Immunotherapy; ICIK
• ISSN: 1559-131X; 1357-0560; 1559-131X
• DOI: 10.1007/s12032-023-02235-y

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.