Prior Exposure to Coxsackievirus A21 Does Not Mitigate Oncolytic Therapeutic Efficacy

Oncolytic viruses (OVs) are being developed as a type of immunotherapy and have demonstrated durable tumor responses and clinical efficacy. One such OV, Coxsackievirus A21 (CVA21), exhibited therapeutic efficacy in early phase clinical trials, demonstrating the ability to infect and kill cancer cells and stimulate anti-tumor immune responses. However, one of the major concerns in using this common cold virus as a therapeutic is the potential for innate and adaptive immune responses to mitigate the benefits of viral infection, particularly in individuals that have been exposed to coxsackievirus prior to treatment. In this study, we assess melanoma responses to CVA21 in the absence or presence of prior exposure to the virus. Melanomas were transplanted into naïve or CVA21-immunized C57BL6 mice and the mice were treated with intratumoral (IT) CVA21. We find that prior exposure to CVA21 does not dramatically affect tumor responses, nor does it alter overall survival. Our results suggest that prior exposure to coxsackievirus is not a critical determinant of patient selection for IT CVA21 interventions.

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The intersection between viral oncolysis, drug resistance, and autophagy

Biological Chemistry ◽

10.1515/hsz-2015-0147 ◽

2015 ◽

Vol 396 (12) ◽

pp. 1269-1280 ◽

Cited By ~ 7

Author(s):

Vladimir Beljanski ◽

Cindy Chiang ◽

John Hiscott

Keyword(s):

Immune Responses ◽

Cancer Treatment ◽

Cancer Survival ◽

Oncolytic Viruses ◽

Clinical Implementation ◽

Viral Lysis ◽

Adaptive Immune Responses ◽

Adaptive Immune ◽

Survival Mechanisms

Abstract Resistance to both cytotoxic and targeted therapies is a major problem facing cancer treatment. The mechanisms of resistance to unrelated drugs share many common features, including up-regulation of detoxifying pathways, activation of pro-survival mechanisms, and ineffective induction of cell death. Oncolytic viruses (OVs) are promising biotherapeutics for cancer treatment that specifically replicate in and lyse cancer cells. In addition to direct viral lysis, the anti-tumor effects of OVs are mediated via innate and adaptive immune responses, and several adaptation mechanisms such as autophagy appear to contribute to their anti-tumor properties. Autophagy is a versatile pathway that plays a key role in cancer survival during stressful conditions such as starvation or cytotoxic drug challenges. Autophagy also plays a role in mediating innate and adaptive immune responses by contributing to antigen presentation and cytokine secretion. This role of autophagy in regulation of immune responses can be utilized to design therapeutic combinations using approaches that either stimulate or block autophagy to potentiate therapeutic efficacy of OVs. Additional studies are needed to determine optimal multimodal combination approaches that will facilitate future successful clinical implementation of OV-based therapies.

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Highlights of Immunomodulation in Salmonella-Based Cancer Therapy

Biomedicines ◽

10.3390/biomedicines9111566 ◽

2021 ◽

Vol 9 (11) ◽

pp. 1566

Author(s):

Christian R. Pangilinan ◽

Che-Hsin Lee

Keyword(s):

Clinical Trials ◽

Cancer Therapy ◽

Immune Responses ◽

Therapeutic Interventions ◽

Cytokine Therapy ◽

Immunomodulatory Effects ◽

Adaptive Immune Responses ◽

Model Studies ◽

Adaptive Immune ◽

Early Phase Clinical Trials

Bacteria-mediated cancer therapy (BMCT) is an emerging tool that may advance potential approaches in cancer immunotherapy, whereby tumors are eradicated by the hosts’ immune system upon recruitment and activation by bacteria such as Salmonella. This paper provides an emphasis on the immunomodulatory effects that encompasses both the innate and adaptive immune responses inherently triggered by Salmonella. Furthermore, modifications of Salmonella-based treatment in the attempt to improve tumor-specific immune responses including cytokine therapy, gene therapy, and DNA vaccine delivery are likewise discussed. The majority of the findings described herein incorporate cell-based experiments and murine model studies, and only a few accounts describe clinical trials. Salmonella-based cancer therapy is still under development; nonetheless, the pre-clinical research and early-phase clinical trials that have been completed so far have shown promising and convincing results. Certainly, the continuous development of, and innovation on, Salmonella-based therapy could pave the way for its eventual emergence as one of the mainstream therapeutic interventions addressing various types of cancer.

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