Antitumor effects of two newly constructed oncolytic herpes simplex viruses against renal cell carcinoma

Area of Science:

• Oncolytic virotherapy
• Cancer research
• Virology

Background:

• Conditionally replicating herpes simplex viruses (HSVs) show potential for treating solid tumors like renal cell carcinoma (RCC).
• First-generation HSVs require enhancement for improved oncolytic capabilities.

Purpose of the Study:

• To evaluate the in vitro and in vivo antitumor effects of two novel oncolytic HSV constructs, Synco-2D and FusOn-H2, against RCC.
• To compare the efficacy of these new constructs against a first-generation oncolytic HSV (Baco-1).

Main Methods:

• Development of two enhanced HSV constructs: Synco-2D (HSV-1 derived, cell fusion induction) and FusOn-H2 (HSV-2 derived, Ras pathway targeting, cell fusion, apoptosis induction).
• In vitro lysis of human RCC cells by Synco-2D, FusOn-H2, and Baco-1.
• In vivo studies in nude mice with xenografted human RCC, administering viruses intratumorally or intravenously.
• Monitoring of tumor growth rate and animal survival post-treatment.

Main Results:

• Both Synco-2D and FusOn-H2 demonstrated significantly higher lysis of human RCC cells in vitro compared to Baco-1.
• A single intratumoral injection of Synco-2D or FusOn-H2 yielded striking antitumor effects against xenografted RCC, outperforming Baco-1's moderate activity.
• Two intravenous injections of Synco-2D inhibited RCC xenograft growth, whereas Baco-1 showed no measurable effect via this route.

Conclusions:

• The newly engineered oncolytic HSVs, Synco-2D and FusOn-H2, exhibit potent antitumor activity against established RCC in preclinical models.
• These findings support the potential of these enhanced HSVs as novel therapeutic agents for RCC.
• Clinical trials are warranted to validate the efficacy of Synco-2D and FusOn-H2 in cancer patients.