ArticlePharmaceutical research2024
Exploring Multivalency in the Development of Anti-PD-L1 Peptides for Cancer Immunotherapy.
Article in Pharmaceutical research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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11 authors.
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Abstract
purposeThe PD-1/PD-L1 pathway is one of the most effective immune checkpoint pathways utilized for cancer immunotherapy. Despite the success of anti-PD-1/PD-L1 mAbs, there is growing interest in developing low molecular weight anti-PD-1/PD-1 agents, such as peptides, because of their improved tumor penetration. We recently developed a small anti-PD-L1 peptide and demonstrated its promising anti-tumor activity. In this study, we investigate multivalency as a strategy to increase the binding avidity and blocking efficiency of the anti-PD-L1 peptide.
methodsMultivalent peptide inhibitors are designed with multiple copies of a peptide inhibitor in a single molecule. We synthesized peptides with different valences and examined their activity. We also investigated how spacer length affects the activity of these multivalent peptides.
resultsUsing this strategy, we developed a multivalent peptide that demonstrated approximately 40 times higher blocking efficiency and improved stability compared to the original peptide. Increasing the valency enhanced the peptide's specificity, which is essential for minimizing side effects.
conclusionsMultivalency approach represents a promising platform for improving the efficacy of peptide-based checkpoint inhibitors.
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