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Recombinant Orthopoxvirus Primes Colon Cancer for Checkpoint Inhibitor and Cross-Primes T Cells for Antitumor and

Sang-In Kim1, Anthony K Park2, Shyambabu Chaurasiya1

  • 1Department of Immuno-Oncology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California.

Molecular Cancer Therapeutics
|December 2, 2020
PubMed

Insights

Oncolytic virus CF33 enhances anti-tumor immunity by increasing T cell activation and immune cell infiltration. Combining CF33 with anti-PD-L1 therapy leads to durable tumor regression and long-term survival in colon cancer models.

Area of Science:

  • Oncology
  • Virology
  • Immunology

Background:

  • Oncolytic viruses can modulate the tumor microenvironment and recruit immune cells.
  • The impact of antiviral immune responses on anti-tumor immunity is not fully understood across different viral platforms and cancer types.

Purpose of the Study:

  • To investigate the efficacy of CF33 oncolytic virus derivatives, alone and in combination with anti-PD-L1, in mouse models of colon cancer.
  • To elucidate the mechanisms by which CF33 influences the anti-tumor immune response.

Main Methods:

  • Testing CF33 derivatives with and without anti-PD-L1 in mouse colon cancer models.
  • Analyzing immune cell infiltration, PD-L1 expression, and T cell activation (CD8+, IFNγ+) in tumors.
  • Evaluating tumor regression, survival, and response to tumor rechallenge.

Main Results:

  • CF33 infection upregulated PD-L1 expression and increased lymphocyte and macrophage infiltration in tumors.
  • Active CD8+ T cell levels were higher in virus-treated tumors.
  • Combination therapy of CF33 derivatives and anti-PD-L1 resulted in durable tumor regression and long-term survival.
  • T cell activation was more robust against viral antigens than tumor antigens in an MHC-I-dependent manner.

Conclusions:

  • CF33 derivatives are effective against colon cancer and enhance anti-tumor immunity.
  • Combination therapy with anti-PD-L1 promotes durable tumor regression and survival.
  • Cross-priming of T cells against viral and tumor antigens may be crucial for the success of viroimmunotherapy.

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