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A Novel Recombinant Fcγ Receptor-Targeted Survivin Combines with Chemotherapy for Efficient Cancer Treatment

Chiao-Chieh Wu1, Chen-Yi Chiang1, Shih-Jen Liu1,2,3

  • 1National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 35053, Taiwan.

Biomedicines
|August 6, 2021
PubMed

Insights

Recombinant survivin-FLIPr fusion protein (rSur-FLIPr) effectively targets Fcγ receptors, enhancing anti-tumor immunity. This novel cancer therapy shows promise, even with prior anti-FLIPr antibodies, and benefits from combination chemotherapy.

Area of Science:

  • Immunology
  • Oncology
  • Biotechnology

Background:

  • Formyl peptide receptor-like 1 inhibitor (FLIPr) acts as an Fcγ receptor (FcγR) antagonist, useful for antigen delivery.
  • Survivin is a tumor-associated antigen overexpressed in various human cancers.

Purpose of the Study:

  • To investigate the potential of recombinant survivin-FLIPr fusion protein (rSur-FLIPr) as a cancer therapeutic.
  • To evaluate the immunogenicity and efficacy of rSur-FLIPr in stimulating anti-tumor immune responses.

Main Methods:

  • Fusion protein construction and characterization (rSur-FLIPr).
  • Assessment of FcγR binding and dendritic cell uptake in vivo.
  • Evaluation of survivin-specific immune responses and tumor suppression.
  • Analysis of immune pathways (TAP-mediated, CD8-dependent) and effect of pre-existing antibodies.
  • Combination therapy with chemotherapy.

Main Results:

  • rSur-FLIPr effectively binds to FcγRs and is taken up by dendritic cells.
  • rSur-FLIPr alone induces survivin-specific immune responses that suppress tumor growth.
  • Antitumor immunity is mediated through TAP-dependent and CD8-dependent pathways.
  • Pre-existing anti-FLIPr antibodies do not inhibit the induced antitumor responses.
  • Combination therapy with chemotherapy significantly benefits tumor-bearing mice.

Conclusions:

  • FLIPr serves as an effective and reusable antigen delivery vector.
  • rSur-FLIPr demonstrates potential as an efficient cancer therapy, alone or in combination with chemotherapy.
Keywords:
Fcγ receptorcancer vaccineformyl peptide receptor-like 1 inhibitorimmunotherapysurvivin

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