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

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Immune checkpoint blockade targeting the programmed cell death protein 1 (PD-1) and its ligand PD-L1 is a key cancer immunotherapy strategy.
• Previous research identified nABPD1 as a molecule that competes with PD-L1 for PD-1 binding.

Purpose of the Study:

• To evaluate the in vitro and in vivo efficacy and safety of novel peptide-conjugated immune cells for cancer immunotherapy.
• To assess the potential of peptide-cell conjugates (PCCs) in enhancing anti-tumor responses, particularly in T-cell acute lymphoblastic leukemia (T-ALL).

Main Methods:

• Synthesis of nABPD1 derivatives, SBP1 and SBP2.
• Assessment of peptide binding efficiency to PD-1-positive cytokine-induced killer (ICIK) cells.
• Evaluation of the cytotoxicity of peptide-conjugated ICIK cells against T-ALL cells in vitro.
• In vivo efficacy studies using T-ALL xenograft mouse models, including fluorescence imaging and organ toxicity assessment.

Main Results:

• SBP1 and SBP2 demonstrated high binding efficiencies (98% and 82%) to ICIK cells.
• Conjugation with SBP1 or SBP2 doubled the cytotoxicity of ICIK cells against T-ALL cells compared to unconjugated ICIK cells.
• In vivo studies showed a >95% reduction in leukemia cell fluorescence in T-ALL xenograft models, indicating enhanced therapeutic effects.
• Morphological evaluations confirmed no significant toxicity of the peptides to major organs.

Conclusions:

• Peptide-cell conjugates (PCCs) represent a promising novel approach to enhance cancer immunotherapy.
• This strategy effectively improves the anti-tumor efficacy of ICIK cells by blocking PD-1, with potential applications for T-ALL patients.