PD-L1 targeted peptide demonstrates potent antitumor and immunomodulatory activity in cancer immunotherapy

Front Immunol. 2024 Apr 30:15:1367040. doi: 10.3389/fimmu.2024.1367040. eCollection 2024.

Abstract

Background: In recent years, immunotherapy has been emerging as a promising alternative therapeutic method for cancer patients, offering potential benefits. The expression of PD-L1 by tumors can inhibit the T-cell response to the tumor and allow the tumor to evade immune surveillance. To address this issue, cancer immunotherapy has shown promise in disrupting the interaction between PD-L1 and its ligand PD-1.

Methods: We used mirror-image phage display technology in our experiment to screen and determine PD-L1 specific affinity peptides (PPL-C). Using CT26 cells, we established a transplanted mouse tumor model to evaluate the inhibitory effects of PPL-C on tumor growth in vivo. We also demonstrated that PPL-C inhibited the differentiation of T regulatory cells (Tregs) and regulated the production of cytokines.

Results: In vitro, PPL-C has a strong affinity for PD-L1, with a binding rate of 0.75 μM. An activation assay using T cells and mixed lymphocytes demonstrated that PPL-C inhibits the interaction between PD-1 and PD-L1. PPL-C or an anti-PD-L1 antibody significantly reduced the rate of tumor mass development in mice compared to those given a control peptide (78% versus 77%, respectively). The results of this study demonstrate that PPL-C prevents or retards tumor growth. Further, immunotherapy with PPL-C enhances lymphocyte cytotoxicity and promotes proliferation in CT26-bearing mice.

Conclusion: PPL-C exhibited antitumor and immunoregulatory properties in the colon cancer. Therefore, PPL-C peptides of low molecular weight could serve as effective cancer immunotherapy.

Keywords: PD-L1 binding peptide; PPL-C; colon cancer; immune checkpoint inhibitors; immunotherapy.

MeSH terms

  • Animals
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • B7-H1 Antigen* / antagonists & inhibitors
  • Cell Line, Tumor
  • Cell Surface Display Techniques
  • Colonic Neoplasms* / therapy
  • Female
  • Humans
  • Immune Checkpoint Inhibitors*
  • Immunologic Factors* / chemistry
  • Immunologic Factors* / pharmacology
  • Immunologic Factors* / therapeutic use
  • Immunotherapy* / methods
  • Mice
  • Mice, Inbred BALB C
  • Peptides* / pharmacology
  • Peptides* / therapeutic use
  • Programmed Cell Death 1 Receptor* / antagonists & inhibitors

Substances

  • Immunologic Factors
  • Antineoplastic Agents
  • Immune Checkpoint Inhibitors
  • B7-H1 Antigen
  • Peptides
  • Programmed Cell Death 1 Receptor

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article. This work was supported by the Major National Projects for Infectious Diseases Research (2008ZX10002002, 2012ZX10002-006-002-003) and the New Drug Research & Development (2009ZX0913-710) and the National High Technology Research and Development Program of China (2011AA02A114), the National Natural Science Foundation of China (30571650, 31370927), and project of the Science and Technology Commission of Shanghai (13431900602). Fudan Medical Cell Rehabilitation University-Enterprise Joint Research Center (SGH1322231).