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Updated: Jul 15, 2025
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Preclinical safety assessment of an oncolytic herpes simplex virus type 2 expressed PD-L1/CD3 bispecific antibody
Yang Wang1, Runyang Wang1, Han Hu1
1National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Hubei University of Technology, Wuhan, China.
Abstract:
Oncolytic virotherapy is an emerging and safe therapeutic approach based on the inherent cytotoxicity of oncolytic viruses and their ability to replicate and spread within tumors in a selective manner. We constructed a new type of oncolytic herpes simplex virus armed with Bispecific Antibody (BsAb) molecules targeting PD-L1/CD3 (oHSV2-PD-L1/CD3-BsAb) to treat human malignancies. We demonstrated the anti-tumor efficacy of oHSV2-PD-L1/CD3-BsAb. To move forward with clinical trials of oHSV2-PD-L1/CD3-BsAb, we conducted a comprehensive preclinical safety evaluation, including hemolysis test, anaphylaxis test, repeated dose toxicity test in cynomolgus monkeys, biodistribution in cynomolgus monkeys and tissue cross-reactivity of PD-L1/CD3-BsAb with human and cynomolgus monkey tissues in vitro. Our preclinical safety evaluation indicated that oHSV2-PD-L1/CD3-BsAb is safe and suitable for clinical trials. After undergoing a thorough evaluation by the United States Food and Drug Administration (FDA), oHSV2-PD-L1/CD3-BsAb has successfully obtained approval to initiate Phase I clinical trials in the United States (FDA IND: 28717).
Insights
A novel oncolytic herpes simplex virus (oHSV2-PD-L1/CD3-BsAb) engineered to target PD-L1/CD3 shows potent anti-tumor efficacy. Comprehensive preclinical safety evaluations confirm its suitability for human clinical trials.
Area of Science:
- Oncolytic virotherapy
- Immunotherapy
- Viral oncology
Background:
- Oncolytic virotherapy utilizes viruses for selective tumor cell destruction.
- Bispecific antibodies (BsAb) enhance immune responses against cancer.
Purpose of the Study:
- To develop and evaluate a novel oncolytic herpes simplex virus (oHSV2) armed with PD-L1/CD3 bispecific antibodies (BsAb).
- To assess the preclinical safety and efficacy of oHSV2-PD-L1/CD3-BsAb for treating human malignancies.
Main Methods:
- Construction of oHSV2-PD-L1/CD3-BsAb.
- In vitro and in vivo anti-tumor efficacy studies.
- Preclinical safety assessments including hemolysis, anaphylaxis, toxicity, and biodistribution in cynomolgus monkeys.
- In vitro tissue cross-reactivity analysis.
Main Results:
- Demonstrated significant anti-tumor efficacy of oHSV2-PD-L1/CD3-BsAb.
- Preclinical safety evaluations indicated the agent is safe and suitable for clinical trials.
- Received FDA approval for Phase I clinical trials.
Conclusions:
- oHSV2-PD-L1/CD3-BsAb is a promising oncolytic virus therapy for human cancers.
- The comprehensive safety data supports its advancement into clinical testing.
- The therapy has successfully gained regulatory approval for Phase I trials.
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