Abstract 4440: Efficacy of Gen-1, an interleukin-12 immune gene therapy, at different dose frequencies

Introduction: The purpose of this study was to investigate the effect of dosing frequency on the antitumor activity of intraperitoneal GEN-1, an interleukin-12 (IL-12) immune gene therapy in a mouse model of peritoneally disseminated ovarian cancer. Procedures: Three GEN-1 dosing regimens were examined for efficacy in ID-8 tumor-bearing mice: weekly, every 2 weeks and every 3 weeks. 2.5 million cancer cells were bolus injected into 4 groups (B, C, and D) of 10 mice each. A control group (A) of 6 mice had PBS injected IP without tumor and an untreated control (E) of 15 mice were injected with 2.5 million cancer cells. Groups B, C, and D were injected with GEN-1 IP weekly, every 2 weeks, and every 3 weeks respectively. Six animals from each group B, C, and D were harvested for translational research (TR) after 5 weekly, 3 every 2-week and 2 every 3-week treatments respectively. The remaining 4 animals in each group were followed for weight change (tumor burden) and survival. Additionally, TR evaluated change in ascites T-cell, B-cell and myeloid cell populations. Results: There was a gradual rise in tumor burden and mortality in all treatment groups with comparable rate between once every week and once every 2-week regimens. Once every 3-week regimen had relatively higher mortality rate and higher tumor burden. There were similar or higher increases in T-cell and B-cells with reduced treatment frequency with lesser increases in myeloid cell density with reduced treatment frequency. Conclusions: Once every 2-week dosing of GEN-1 in human studies is warranted. Future combination studies of Gen-1 with immune checkpoint inhibitors will evaluate the safety and efficacy of this regimen. Citation Format: Subeena Sood, Jean D. Boyer, Jessica Kim, Majed M. Matar, Olivia Signer, Jennifer S. Rice, Alanna M. Smith, Nicholas Borys, Khursheed Anwer. Efficacy of Gen-1, an interleukin-12 immune gene therapy, at different dose frequencies. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4440.