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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Modulation of the Intratumoral Immune Landscape by Oncolytic Herpes Simplex Virus Virotherapy
Jie Yin1,2, James M Markert1,3,4, Jianmei W Leavenworth1,2
1Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, AL, United States.
Abstract:
Vaccines and immunotherapeutic approaches to cancers with the advent of immune checkpoint inhibitors and chimeric antigen receptor-modified T cells have recently demonstrated preclinical success and entered clinical trials. Despite advances in these approaches and combinatorial therapeutic regimens, depending on the nature of the cancer and the immune and metabolic landscape within the tumor microenvironment, current immunotherapeutic modalities remain inadequate. Recent clinical trials have demonstrated clear evidence of significant, and sometimes dramatic, antitumor activity, and long-term survival effects of a variety of oncolytic viruses (OVs), particularly oncolytic herpes simplex virus (oHSV). Acting as a multifaceted gene therapy vector and potential adjuvant-like regimens, oHSV can carry genes encoding immunostimulatory molecules in its genome. The oncolytic effect of oHSV and the inflammatory response that the virus stimulates provide a one-two punch at attacking tumors. However, mechanisms underlying oHSV-induced restoration of intratumoral immunosuppression demand extensive research in order to further improve its therapeutic efficacy. In this review, we discuss the current OV-based therapy, with a focus on the unique aspects of oHSV-initiated antiviral and antitumor immune responses, arising from virus-mediated immunological cell death to intratumoral innate and adaptive immunity.
Insights
Oncolytic viruses (OVs), especially oncolytic herpes simplex virus (oHSV), show promise in cancer treatment by directly killing tumors and stimulating immune responses. Further research is needed to optimize oHSV therapy for enhanced antitumor effects.
Area of Science:
- Immunology
- Oncology
- Virology
Background:
- Cancer immunotherapies like checkpoint inhibitors and CAR T-cells show promise but face limitations due to tumor microenvironment factors.
- Oncolytic viruses (OVs), particularly oncolytic herpes simplex virus (oHSV), have demonstrated significant antitumor activity and long-term survival benefits in clinical trials.
Purpose of the Study:
- To review current oncolytic virus (OV) therapy, focusing on oncolytic herpes simplex virus (oHSV).
- To explore the unique antiviral and antitumor immune responses initiated by oHSV.
- To highlight the need for research into mechanisms of oHSV-induced restoration of intratumoral immunosuppression to improve therapeutic efficacy.
Main Methods:
- Review of current literature on oncolytic virus therapy.
- Focus on oncolytic herpes simplex virus (oHSV) as a gene therapy vector and adjuvant.
- Analysis of virus-mediated immunological cell death and immune responses.
Main Results:
- oHSV acts as a multifaceted gene therapy vector, carrying immunostimulatory genes.
- The oncolytic effect of oHSV combined with virus-stimulated inflammation provides a dual-action antitumor strategy.
- oHSV can induce immunological cell death and stimulate innate and adaptive immunity within the tumor microenvironment.
Conclusions:
- oHSV demonstrates significant potential in cancer immunotherapy through direct oncolysis and immune stimulation.
- Understanding and overcoming oHSV-induced intratumoral immunosuppression is crucial for enhancing therapeutic outcomes.
- Further research into oHSV-mediated immune responses is essential for advancing cancer treatment strategies.
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