Abstract IA27: Combinatorial immunotherapy using whole tumor antigen: Evidence from phase I trials

Novel therapeutic strategies are warranted in recurrent ovarian cancer. We report two independent consecutive studies of combinatorial immunotherapy comprising dendritic cell (DC)-based autologous whole tumor antigen vaccination in combination with antiangiogenesis therapy. Thirty one patients with recurrent progressive stage III and IV ovarian cancer with available tumor lysate from debulking surgery enrolled in two different vaccination studies. First six underwent priming with intravenous bevacizumab and oral metronomic cyclophosphamide followed by vaccination with an autologous DC preparation pulsed with freeze-thaw autologous tumor lysate while the other 25 underwent vaccination with an enhanced vaccine of autologous DCs loaded with HOCl-oxidized autologous tumor lysate administered intranodally in combination with antiangiogenesis therapy. Both studies were followed by lymphodepletion and transfer of autologous vaccine-primed, ex vivo CD3/CD28-costimulated peripheral blood T-cells, in combination with antiangiogenesis therapy and vaccination. Feasibility, safety, biological and clinical efficacy were evaluated. Eleven patients have completed vaccination and T cell transfer to date, while twenty-three additional patients completed vaccination only. Vaccination was well tolerated and elicited tumor-specific T cell responses against various ovarian tumor antigens. Preliminary results demonstrate that patients9 DCs loaded with HOCl-oxidized lysate elicited strong tumor-specific IFN-gamma; secretions and produced high levels of Th1-priming cytokines and chemokines, including IL-12. A clinical benefit of 65% correlated with the immune response with some patients experiencing prolonged progression free survival. Following lymphodepletion, adoptive transfer of vaccine-primed T-cells was well tolerated and resulted in durable reduction of T-regulatory cells and restoration of vaccine-induced antitumor immunity in patients who experienced clinical benefit. One patient exhibited a complete response at end of study and stable disease was observed in 7 out of the 11 patients who completed vaccination and T cell transfer. Data on additional patients will be presented at the meeting. Our results suggest the use of combinatorial cellular immunotherapy comprising DC vaccination with whole tumor antigen and adoptive lymphocyte transfer using tumor antigen-specific T cells for the treatment of patients with recurrent ovarian cancer is promising yet warrants further investigation. Citation Format: Lana E. Kandalaft, Janos Tanyi, Cheryl Chiang, George Coukos. Combinatorial immunotherapy using whole tumor antigen: Evidence from phase I trials. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr IA27.