Oncolytic HSV-1 virotherapy: clinical experience and opportunities for progress

Area of Science:

• Oncology
• Virology
• Gene Therapy

Background:

• Oncolytic virotherapy utilizes engineered viruses to selectively target and destroy cancer cells.
• Herpes simplex virus (HSV) type 1 mutants have demonstrated preclinical antitumor activity.
• Clinical trials have assessed the safety and efficacy of HSV-based oncolytic viruses in various cancers.

Purpose of the Study:

• To review the clinical experience of oncolytic virotherapy with HSV mutants.
• To discuss biological factors limiting HSV infection and spread in tumors.
• To explore novel strategies for enhancing the antitumor efficacy of HSV-based virotherapy.

Main Methods:

• Systematic review of published clinical trial data for HSV-based oncolytic virotherapy.
• Analysis of biological mechanisms influencing virus-host interactions in cancer.
• Discussion of emerging therapeutic approaches to augment oncolytic virus performance.

Main Results:

• HSV mutants are safe for clinical use across diverse cancer types.
• While some studies suggest prolonged survival compared to historical controls, significant clinical responses have been infrequent.
• Preclinical models show substantial antitumor effects, contrasting with limited clinical dramatic responses.

Conclusions:

• Oncolytic virotherapy with HSV mutants is safe but requires optimization for greater clinical impact.
• Understanding and overcoming biological barriers to virus replication and spread is crucial.
• Development of enhanced HSV vectors and combination therapies holds promise for improving treatment outcomes.