Abstract PR15: Autologous whole-tumor antigen combinatorial immunotherapy for recurrent ovarian cancer.

Abstract

Abstract 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. Twenty-one patients with recurrent progressive stage III and IV ovarian cancer with available tumor lysate from secondary debulking surgery enrolled in two different studies. First 6 underwent priming with intravenous bevacizumab and oral metronomic cyclophosphamide (bev/cy x 2 doses), followed by vaccination with an autologous DC preparation pulsed with freeze-thaw autologous tumor lysate while the other fifteen underwent vaccination with an enhanced more immunogenic vaccine where autologous DCs were loaded with HOCl-oxidized autologous tumor lysate administered intranodally every 2 weeks in combination with intravenous bev. Both studies were followed by lymphodepletion using high-dose outpatient cyclophosphamide and fludarabine and transfer of 5-30 x10e9 autologous vaccine-primed, ex vivo CD3/CD28-costimulated peripheral blood T cells, in combination with antiangiogenesis therapy and vaccination. Feasibility, safety, and biological and clinical efficacy were evaluated. Eight subjects have completed vaccination and T cell transfer to date, while thirteen additional subjects completed vaccination only. Vaccination was well tolerated and produced limited grade 1 toxicities and elicited tumor-specific T cell responses against various ovarian tumor antigen in both studies and clinical responses correlated with the immune response with ~66% of patients achieving clinical benefit with some experiencing prolonged progression free survival and remission inversion. Following lymphodepletion, adoptive transfer of vaccine-primed, CD3/CD28-costimulated autologous T cells produced grade 1 toxicity and resulted in durable reduction of CD4+FoxP3+ T regulatory cells, increased total lymphocyte counts and restoration of vaccine-induced antitumor immunity in patients who experienced clinical benefit at end of study. One patient exhibited no evidence of disease at end of study. Stable disease was observed in three subjects to date. Interestingly in a subject where adoptive T cell transfer was not followed by restoration of vaccine-induced antitumor immunity, disease progression was observed. 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. This abstract is also presented as Poster A30. Citation Format: Lana E. Kandalaft, Janos Tanyi, Cheryl Lai-Lai Chiang, Drew Torigian, Daniel J. Powell, Jr., George Coukos. Autologous whole-tumor antigen combinatorial immunotherapy for recurrent ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr PR15.