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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Oncolytic HSV Vectors and Anti-Tumor Immunity
Joseph C Glorioso1, Justus B Cohen1, William F Goins1
1Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA , USA.
Abstract:
The therapeutic promise of oncolytic viruses (OVs) rests on their ability to both selectively kill tumor cells and induce anti-tumor immunity. The potential of tumors to be recognized and eliminated by an effective anti-tumor immune response has been spurred on by the discovery that immune checkpoint inhibition can overcome tumor-specific cytotoxic T cell (CTL) exhaustion and provide durable responses in multiple tumor indications. OV-mediated tumor destruction is now recognized as a powerful means to assist in the development of anti-tumor immunity for two important reasons: (i) OVs, through the elicitation of an anti-viral response and the production of type I interferon, are potent stimulators of inflammation and can be armed with transgenes to further enhance anti-tumor immune responses; and (ii) lytic activity can promote the release of tumor-associated antigens (TAAs) and tumor neoantigens that function as in situ tumor-specific vaccines to elicit adaptive immunity. Oncolytic herpes simplex viruses (oHSVs) are among the most widely studied OVs for the treatment of solid malignancies, and Amgen's oHSV Imlygic® for the treatment of melanoma is the only OV approved in major markets. Here we describe important biological features of HSV that make it an attractive OV, clinical experience with HSV-based vectors, and strategies to increase applicability to cancer treatment.
Insights
Oncolytic viruses (OVs) selectively kill tumor cells and stimulate anti-tumor immunity. Oncolytic herpes simplex viruses (oHSVs) show promise for cancer treatment by enhancing immune responses and releasing tumor antigens.
Area of Science:
- Virology
- Immunology
- Oncology
Background:
- Oncolytic viruses (OVs) offer dual therapeutic action: direct tumor cell killing and induction of anti-tumor immune responses.
- Immune checkpoint inhibitors have demonstrated efficacy by overcoming tumor-induced T cell exhaustion.
- OV-mediated tumor lysis releases tumor-associated antigens (TAAs), acting as in situ vaccines to promote adaptive immunity.
Purpose of the Study:
- To explore the therapeutic potential of oncolytic viruses (OVs) in cancer treatment.
- To highlight the advantages of oncolytic herpes simplex viruses (oHSVs) as OV vectors.
- To review clinical experiences and strategies for enhancing HSV-based OV cancer therapy.
Main Methods:
- Review of biological features of herpes simplex virus (HSV) relevant to OV therapy.
- Analysis of clinical data and outcomes for HSV-based OV treatments.
- Discussion of strategies for improving the efficacy and applicability of oHSVs in cancer.
Main Results:
- OVs stimulate inflammation and can be engineered to enhance anti-tumor immunity.
- Tumor destruction by OVs facilitates the release of TAAs, priming adaptive immune responses.
- Oncolytic herpes simplex viruses (oHSVs) are extensively studied, with one approved therapy for melanoma.
Conclusions:
- HSV possesses inherent biological characteristics that make it a suitable candidate for OV development.
- Clinical application of HSV-based OVs is expanding, with ongoing research focused on optimizing their use.
- Further strategies are needed to broaden the application of oHSVs across various cancer types.
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