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April 5, 2026Cancer Research0 citations

Novel Targeted Protein Degradation Platform Using Internalization-Enhancing Peptide for...

Abstract 992: A novel targeted protein degradation platform based on internalization-enhancing peptide for lysosomal degradation of cell-surface proteins

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Authors

DKDae Young KimDSDahye SimDPDaeho Park

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Overview

Demonstrates that internalization-enhancing peptide promotes lysosomal degradation of PD-L1 in diverse tumor cells, suggesting a new therapeutic strategy.

Key Points

  • To explore a novel platform for targeted protein degradation using internalization-enhancing peptides to enhance lysosomal degradation of cell-surface proteins.
  • Used a novel internalization-enhancing peptide (IEP) to facilitate internalization of antibodies.
  • Tested the effects of IEP on Atezolizumab (ATZ) and Durvalumab (DUR) with PD-L1 as a target.
  • Assessed lysosomal degradation using BafA1 and MG132 inhibitors to differentiate pathways.
  • Conducted experiments in MDA-MB-231 (TNBC) and HCC827 (NSCLC) cells to evaluate general applicability.
  • Significant reduction of PD-L1 levels was observed in cells treated with the ATZ-IEP complex compared to ATZ or IEP alone.
  • Degradation of PD-L1 was confirmed to be lysosomal, as indicated by BafA1 inhibition.
  • IEP showed similar efficacy with Durvalumab, indicating broad applicability.
  • Reduction in PD-L1 was more substantial in cells with lower baseline PD-L1 expression.

Cite This Study

Kim et al. (2026) studied this question.

synapsesocial.com/papers/69d1fcc0a79560c99a0a269dhttps://doi.org/10.1158/1538-7445.am2026-992
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