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Related Concept Videos

  1. Home
  3. Research Domains
  5. Biomedical And Clinical Sciences
  7. Oncology And Carcinogenesis
  9. Predictive And Prognostic Markers
  11. Enhancing Anti-cancer Immune Response By Acidosis-sensitive Nanobody Display.
  1. Home
  3. Research Domains
  5. Biomedical And Clinical Sciences
  7. Oncology And Carcinogenesis
  9. Predictive And Prognostic Markers
  11. Enhancing Anti-cancer Immune Response By Acidosis-sensitive Nanobody Display.

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Enhancing Anti-Cancer Immune Response by Acidosis-Sensitive Nanobody Display.

Leah E Knepper1, Emily T Ankrom1, Damien Thévenin2

  • 1Department of Chemistry, Lehigh University, Bethlehem, PA, 18015, USA.

The Journal of Membrane Biology
|September 10, 2024

View abstract on PubMed

Summary
This summary is machine-generated.

Targeting cancer

Keywords:
Anticancer agentsPeptidesSingle-domain antibodiesTargeted immunotherapy

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Area of Science:

  • Oncology
  • Immunology
  • Biotechnology

Background:

  • Cancer immunotherapies often rely on tumor-specific biomarkers, which can cause off-target effects and treatment resistance.
  • The acidic tumor microenvironment presents a potential target for cancer therapies, sparing healthy tissues.
  • pH (Low) Insertion Peptide (pHLIP) selectively targets acidic tumor environments for therapeutic applications.

Purpose of the Study:

  • To develop a novel cancer immunotherapy strategy by directly fusing an anti-CD16 nanobody to pHLIP.
  • To leverage the pH-sensitive nature of pHLIP for targeted delivery and activation of immune cells.
  • To assess the efficacy of the pHLIP-nanobody conjugate in activating natural killer (NK) cells and eliminating cancer cells.

Main Methods:

  • Directly fusing an anti-CD16 nanobody to the pH (Low) Insertion Peptide (pHLIP).
Tumor acidosis
  • Utilizing pHLIP's pH-sensitive insertion into cancer cell membranes under acidic conditions.
  • Evaluating the activation of CD16 receptor on effector cells and NK cell-mediated cancer cell destruction in vitro.

    • Main Results:

    • Demonstrated successful insertion of pH-sensitive agents into cancer cells.
    • Confirmed activation of the CD16 receptor on effector cells by the pHLIP-nanobody conjugate.
    • Showcased effective targeting and destruction of cancer cells by CD16+ NK cells in two cancer cell lines.

    Conclusions:

    • Direct fusion of anti-CD16 nanobody to pHLIP offers a promising strategy for cancer immunotherapy.
    • This approach effectively targets the acidic tumor microenvironment and activates NK cells for cancer cell destruction.
    • The pHLIP-nanobody conjugate eliminates the need for antibody recruitment, simplifying the immunotherapy process.