Celsion Corporation announced the publication of data from its Phase 1b OVATION 1 Study with GEN-1 in combination with neoadjuvant chemotherapy (NACT) in patients with advanced ovarian cancer in Clinical Cancer Research, a journal of the American Association for Cancer Research. The study, authored by Premel H. Thaker, etal. is titled “GEN-1 in Combination with Neoadjuvant Chemotherapy for Patients with Advanced Epithelial Ovarian Cancer: A Phase I Dose-Escalation Study.” GEN-1 is a DNA-based interleukin-12 (IL-12) immunotherapy currently in Phase I/II clinical development for the localized treatment of advanced ovarian cancer (the OVATION 2 Study). GEN-1 is an immunotherapy that produces safe and durable local levels of IL-12, a pluripotent cytokine associated with the stimulation of innate and adaptive immune response against cancer. The GEN-1 nanoparticle comprises a DNA plasmid encoding IL-12 gene and a synthetic polymer facilitating plasmid delivery vector. Premal H. Thaker, M.D., M.S., Professor of Gynecologic Oncology and Director of Gynecologic Oncology Clinical Research at the Washington University School of Medicine at Washington University Medical Center in St. Louis, is the study chair for the OVATION program. The OVATION 1 Study enrolled 18 patients with newly diagnosed stage IIIC and IV epithelial ovarian cancer in a standard 3+3 dose-escalation design testing four GEN-1 doses (36 mg/m2, 47 mg/m2, 61 mg/m2 and 79mg/m2) in combination with NACT (carboplatin-paclitaxel). There were 15 patients evaluable for safety, and 14 underwent interval debulking and were evaluable for Response Evaluation Criteria in Solid Tumors (RECIST). Results from translational studies show the following: A dose-dependent increase in immunostimulatory cytokines IL-12 and its downstream cytokine IFN-? in ascitic fluid. The anticancer effects of these cytokines are widely recognized in human malignancies. The proportion of myeloid dendritic cells in the peritoneal fluid trended higher (3.1-fold) accompanied by a similar 3.0-fold rise in CD8+ cells. GEN-1 appeared to reduce four immunosuppressive signals (Foxp3, IDO1, PD-1 and PD-L1) within the tumor microenvironment, a trend not seen with NAC therapy alone. GEN-1 also appeared to stimulate the body’s immune system through the production of CD4 and CD8 cells. GEN-1 gene therapy was associated with an apparent increase in the cytotoxic state of T cells within the tumor microenvironment as indicated by the increases in the ratios of CD8+/CD4+ and CD8+/Treg cells. Indeed, higher CD8+/CD4+ T cell and CD8+/Treg ratios are considered prognostic for prolonged survival. The Journal of Clinical Cancer Research is a publication of the American Association for Cancer Research. It publishes innovative clinical and translational cancer research studies that bridge the laboratory and the clinic. The Journal is especially interested in clinical trials evaluating new treatments, accompanied by research on pharmacology, and molecular alterations or biomarkers that predict response or resistance to treatment. The Journal also prioritizes laboratory and animal studies of new drugs and molecule-targeted agents with the potential to lead to clinical trials, and studies of targetable mechanisms of oncogenesis, progression of the malignant phenotype and metastatic disease. Epithelial ovarian cancer (EOC) is the 5th deadliest malignancy among women in the United States. There are approximately 22,000 new cases of ovarian cancer every year and the majority (approximately 70%) are diagnosed in advanced stages III and IV. EOC is characterized by dissemination of tumor in the peritoneal cavity with a high risk of recurrence (75%, stage III and IV) after surgery and chemotherapy. Since the 5-year survival rates of patients with stages III and IV disease at diagnosis are poor (41% and 20%, respectively), there remains a need for a therapy that not only reduces the recurrence rate but also improves overall survival. The peritoneal cavity of advanced ovarian cancer patients contains the primary tumor environment and is an attractive target for regional approach to immune modulation.