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Understanding and addressing barriers to successful adenovirus-based virotherapy for ovarian cancer

Cancer Gene Therapy volume 28, pages 375–389 (2021)Cite this article

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Abstract

Ovarian cancer is the leading cause of death among women with gynecological cancer, with an overall 5-year survival rate below 50% due to a lack of specific symptoms, late stage at time of diagnosis and a high rate of recurrence after standard therapy. A better understanding of heterogeneity, genetic mutations, biological behavior and immunosuppression in the tumor microenvironment have allowed the development of more effective therapies based on anti-angiogenic treatments, PARP and immune checkpoint inhibitors, adoptive cell therapies and oncolytic vectors. Oncolytic adenoviruses are commonly used platforms in cancer gene therapy that selectively replicate in tumor cells and at the same time are able to stimulate the immune system. In addition, they can be genetically modified to enhance their potency and overcome physical and immunological barriers. In this review we highlight the challenges of adenovirus-based oncolytic therapies targeting ovarian cancer and outline recent advances to improve their potential in combination with immunotherapies.

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Fig. 1: Barriers to Ad vector delivery.
Fig. 2: Oncolytic Ads help overcoming immunosuppression and boosting anti-tumor immunity in EOC.

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Funding

This study was funded by the Department of Defense Ovarian Cancer Research Program (W81XWH-18-1-0063) and by the NIH (R01CA211096).

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Authors and Affiliations

  1. The Division of Cancer Biology and Biologic Therapeutics Center, Department of Radiation Oncology, School of Medicine, Washington University in Saint Louis, 660 South Euclid Avenue, Campus Box 8224, St. Louis, MO, 63110, USA

    Rebeca Gonzalez-Pastor & David T. Curiel

  2. Department of Surgery, Washington University School of Medicine, Saint Louis, MO, 63110, USA

    Peter S. Goedegebuure

  3. Alvin J. Siteman Cancer Center, 660 S. Euclid Avenue, St. Louis, MO, 63110, USA

    Peter S. Goedegebuure

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  1. Rebeca Gonzalez-Pastor
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  2. Peter S. Goedegebuure
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  3. David T. Curiel
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R.G.-P. did literature research and wrote the paper. P.S.G. and D.T.C. provided supervision.

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Correspondence to David T. Curiel.

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Gonzalez-Pastor, R., Goedegebuure, P.S. & Curiel, D.T. Understanding and addressing barriers to successful adenovirus-based virotherapy for ovarian cancer. Cancer Gene Ther 28, 375–389 (2021). https://doi.org/10.1038/s41417-020-00227-y

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