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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
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Oncolytic Adenovirus and Tumor-Targeting Immune Modulatory Therapy Improve Autologous Cancer Vaccination

Hong Jiang1, Yisel Rivera-Molina2, Candelaria Gomez-Manzano2

  • 1Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas. hjiang@mdanderson.org jfueyo@mdanderson.org.

Cancer Research
|June 2, 2017
PubMed

Insights

Combining oncolytic viruses with immune checkpoint inhibitors creates a potent cancer vaccine. This approach enhances tumor-specific T-cell responses and prolongs survival by overcoming tumor immunosuppression.

Area of Science:

  • Oncolytic virotherapy
  • Cancer immunology
  • Immunotherapy

Background:

  • Oncolytic viruses target tumor cells and stimulate antitumor immunity but have limitations.
  • Immune checkpoint inhibitors (ICIs) show efficacy but cause toxicity due to non-specific T-cell activation.
  • Combining oncolytic viruses and ICIs may offer a more effective and specific cancer therapy.

Purpose of the Study:

  • To develop and evaluate an oncolytic adenovirus expressing OX40 ligand (Delta-24-RGDOX) for cancer therapy.
  • To investigate the synergistic effects of combining Delta-24-RGDOX with anti-PD-L1 therapy in glioma models.

Main Methods:

  • Construction of Delta-24-RGDOX, an oncolytic adenovirus expressing OX40 ligand.
  • Assessment of Delta-24-RGDOX's ability to induce immunogenic cell death and recruit lymphocytes.
  • Evaluation of Delta-24-RGDOX and anti-PD-L1 combination therapy in immunocompetent and immunodeficient mice models.

Main Results:

  • Delta-24-RGDOX induced immunogenic cell death and lymphocyte recruitment.
  • Delta-24-RGDOX demonstrated superior tumor-specific T-cell activation and proliferation compared to its predecessor.
  • Combination therapy with Delta-24-RGDOX and anti-PD-L1 synergistically inhibited gliomas and improved survival.

Conclusions:

  • Oncolytic virus and immune checkpoint modulator combination therapy elicits potent in situ autologous cancer vaccination.
  • This combined strategy results in efficacious, tumor-specific, and long-lasting therapeutic effects.
  • The approach holds promise for overcoming tumor immunosuppression and enhancing cancer treatment outcomes.

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