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Safety of non-replicative and oncolytic replication-selective HSV vectors
Alberto L Epstein1, Samuel D Rabkin2
1EG 427 SAS, 29 Rue du Faubourg Saint Jacques, 75014 Paris, France.
Trends in Molecular Medicine
|June 17, 2024
Summary
Herpes simplex virus type 1 (HSV-1) vectors are promising for gene and cancer therapy. These vectors are well-tolerated, can be re-administered, and show potential for clinical applications.
Area of Science:
- Virology
- Gene Therapy
- Oncolytic Virus Therapy
Background:
- Herpes simplex virus type 1 (HSV-1) is a pathogen utilized for developing therapeutic vectors.
- HSV-1 vectors are classified into replication-selective oncolytic vectors for cancer treatment and defective non-replicative vectors for gene therapy.
- These vectors can carry large genetic payloads (≥30 kb), have undergone clinical trials, and exhibit a favorable safety profile.
Purpose of the Study:
- To review clinical applications of HSV-1 vectors.
- To discuss host-virus immune interactions influencing HSV vector safety and efficacy.
Main Methods:
- Review of clinical data and preclinical studies on HSV-1 vectors.
- Analysis of immunological responses to HSV-1 vectors in clinical settings.
Main Results:
- HSV-1 vectors have been translated to clinical use for cancer and gene therapy.
- Oncolytic HSV (oHSV) replicates in tumors, inducing immune responses while remaining well-tolerated.
- Non-replicative vectors induce limited immune responses.
- Pre-existing HSV-1 immunity does not prevent vector efficacy or re-administration.
Conclusions:
- HSV-1 vectors offer a versatile platform for therapeutic interventions.
- Understanding host-virus immune interactions is crucial for optimizing HSV vector safety and efficacy.
- The potential for re-administration due to non-eliminating immune responses enhances the therapeutic utility of HSV-1 vectors.
