Abstract
Simple SummaryOncolytic Herpes simplex virus-1 (HSV-1) offers the dual potential of both lytic tumor-specific cell killing and inducing anti-tumor immune responses. The HSV-1 genome can be altered to enhance both components and this may be applicable for the treatment of a broad range of cancers. Several engineered oncolytic viruses based on the HSV-1 backbone are currently under investigation in various clinical trials, both as single agents and in combination with various immunomodulatory drugs.Herpes simplex virus 1 (HSV-1) provides a genetic chassis for several oncolytic viruses (OVs) currently in clinical trials. Oncolytic HSV1 (oHSV) have been engineered to reduce neurovirulence and enhance anti-tumor lytic activity and immunogenicity to make them attractive candidates in a range of oncology indications. Successful clinical data resulted in the FDA-approval of the oHSV talimogene laherparepvec (T-Vec) in 2015, and several other variants are currently undergoing clinical assessment and may expand the landscape of future oncologic therapy options. This review offers a detailed overview of the latest results from clinical trials as well as an outlook on newly developed HSV-1 oncolytic variants with improved tumor selectivity, replication, and immunostimulatory capacity and related clinical studies.
Highlights
In the past decade, immunotherapeutic drugs for oncology have revolutionized the field.The landscape of immunotherapeutic drugs has been spearheaded by immune checkpoint inhibition [1,2,3], as well as CAR-T-cell therapy [4,5], suicide-gene approaches [6], and a range of other agents, e.g., tumor antigen vaccinations [7]
This review aims to give an overview over the state of clinical applications of oncolytic viral therapy with Oncolytic HSV1 (oHSV)‐1 and future directions
Herpes simplex virus 1 (HSV-1) based oncolytic viruses (OVs) have shown promising results in various preclinical studies regarding efficacy based on combined tumor cell killing abilities and immunostimulation in a broad range of cancers
Summary
Immunotherapeutic drugs for oncology have revolutionized the field. OVs infect tumor cells and cause their lysis leading to a release of tumor-specific antigens as well as neoantigens. Among OVs in clinical trials, Herpes simplex virus 1 (HSV-1)-derived agents are some of the most widely tested viral vectors and have been thoroughly investigated in numerous pre-clinical studies [8]. Its large genome of 150 kb [11], infectivity, and lytic activity present ideal properties for a potent engineerable OV: HSV-1 can infect a variety of cell types and cause lysis; its comparatively large genome facilitates modifications that can enhance anti-tumorigenic features and reduce neurovirulence [12] and it can be inactivated by the anti-herpetic drugs ganciclovir, acyclovir, or valacyclovir.
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