Abstract 496: Inflammatory responses with infiltrating DC and functional cytotoxic T lymphocytes in the dermal vaccination sites of GVAX/ipilimumab treated prostate cancer patients.

We have been studying the safety and clinical efficacy of the Prostate GVAX vaccine (consisting of two allogeneic GM-CSF secreting tumor cell lines: LNCaP and PC3) and the CTLA-4 blocking antibody ipilimumab in prostate cancer patients in a phase I/II dose escalation/expansion trial. To assess immune reactivity against the GVAX vaccine, immune infiltrate analysis of the vaccination sites was performed. Punch biopsies of the vaccination site were taken 48 hours after the 1 st , 5 th , and 11 th injections and analyzed by immunohistochemical staining. Injection of the GVAX vaccine evoked striking local reactions that were characterized by local erythema, induration and swelling in all patients. Analysis of the vaccination site biopsies revealed that the GVAX/ipilimumab combination resulted in an inflammatory response in the skin with intradermal infiltrates of CD1a+ dendritic cells (DC), DC-SIGN+/CD68+ immature DC/macrophages, CD14+ monocyte-like cells, eosinophils, and of CD4+, CD8+, and Granzyme-B+ T lymphocytes. Strikingly, CD56+ NK cells were completely absent. The inflammatory response significantly increased over the course of treatment and resulted in accelerated clearance of the vaccine in vivo. Moreover, analysis revealed that the PC3 vaccine was more immunogenic, and induced a more potent anti-vaccine T cell response. The latter was confirmed in an in vitro cytotoxicity assay. Upon multiple vaccinations T cell reactivity to PC3 was significantly enhanced in the PC3 but not in the LNCaP vaccination sites, whereas reactivity to LNCaP was not enhanced in either vaccination site. We conclude that the GVAX/ipilimumab combination elicits a local immune infiltrate that increases over time, consistent with an induced CD8+ effector T cell mediated cytolytic response, only in vaccination sites of the PC3 component of the vaccine. Citation Format: Saskia J. Santegoets, Leonieke JJ van Mens, Jeroen AM Belien, Anita GM Stam, Sinead M. Lougheed, Rik J. Scheper, Shabnam Samiei, Helen Gall, Karin Jooss, Jean-Marie Cuillerot, Natalie Sacks, Kirsten Hege, Winald R. Gerritsen, Alfons JM van den Eertwegh, Tanja D. de Gruijl. Inflammatory responses with infiltrating DC and functional cytotoxic T lymphocytes in the dermal vaccination sites of GVAX/ipilimumab treated prostate cancer patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 496. doi:10.1158/1538-7445.AM2013-496