Potent and Targeted Sindbis Virus Platform for Immunotherapy of Ovarian Cancer

Area of Science:

• Oncology
• Immunotherapy
• Viral Vector Technology

Background:

• Developing novel therapeutic strategies for ovarian cancer is critical.
• Sindbis viral (SV) vectors offer a platform for cancer treatment delivery.
• Immunomodulatory agents like IL-12 and OX40 agonists show promise in cancer therapy.

Purpose of the Study:

• To evaluate the efficacy of SV.IL-12 combined with an agonistic OX40 antibody in an ovarian cancer model.
• To investigate the immunological mechanisms underlying the anti-tumor response.
• To develop a combined SV vector (SV.IgGOX40.IL-12) for enhanced local delivery of immunoregulatory agents.

Main Methods:

• Utilized a Mouse Ovarian Surface Epithelial Cell Line (MOSEC) model for ovarian cancer.
• Administered SV.IL-12 and an agonistic OX40 antibody, both as single agents and in combination.
• Developed and tested a single SV vector, SV.IgGOX40.IL-12, encoding both IL-12 and anti-OX40 sequences.
• Assessed tumor elimination, prevention of recurrence, and immune cell infiltration and reprogramming.

Main Results:

• SV.IL-12 combined with an agonistic OX40 antibody demonstrated significant efficacy in eliminating ovarian tumors.
• The combination therapy prevented tumor recurrence in mice rechallenged with cancer cells after 5 months.
• Treatment efficacy was dependent on T-cells, which showed transcriptional and metabolic reprogramming, and led to immune cell influx into the tumor microenvironment.
• The combined SV vector, SV.IgGOX40.IL-12, facilitated local delivery and enhanced the anti-tumor immune response.

Conclusions:

• The combination of SV.IL-12 and an agonistic OX40 antibody is a potent strategy for ovarian cancer treatment.
• SV.IgGOX40.IL-12 enables efficient local delivery of immunomodulatory agents, enhancing anti-tumor immunity.
• This approach shows promise as a safe and effective therapy for various cancer types.