Sipuleucel-T product characterization across different disease states of prostate cancer.

Abstract

42 Background: Sipuleucel-T is an autologous cellular immunotherapy approved for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer (mCRPC). In the Phase 3 mCRPC trials, antigen presenting cell (APC) activation in sipuleucel-T correlated with overall survival. Here product characteristics of sipuleucel-T were compared in patients (pts) from trials in the neoadjuvant (n=42), asymptomatic or minimally symptomatic mCRPC (n=341), and mCRPC (n=104) disease states. Methods: Sipuleucel-T comprises 3 treatments approximately 2 wks apart. Cellular composition and APC activation (CD54 upregulation) were evaluated in all courses of sipuleucel-T, and cumulative CD54 upregulation was calculated for each patient. In some studies, cytokines were assayed from culture supernatants and T cell and B cell activation markers were assessed by flow cytometry during manufacture. Results: Baseline demographics were generally representative of each disease state; neoadjuvant pts were younger with less disease burden; mCRPC pts had the highest disease burden and more frequent prior chemotherapy. While neoadjuvant pts had greater levels of T cells, the patterns of APC activation were similar among all trials, with increased CD54 upregulation at the second and third treatment. The trend for cumulative fold increase in CD54 upregulation was significantly greater in earlier disease pts (neoadjuvant: 35.5, asymptomatic or minimally symptomatic mCRPC: 28.7, mCRPC: 21.8; p<0.0001 (Joncheere-Terpstra test)). During manufacture of the product, lymphocyte activation markers and cytokines consistently showed enhanced expression during the second and third treatments in all disease states. The lymphocyte activation and cytokine profiles were similar between early and later disease state pts. Conclusions: While cellular composition varied with disease state, manufacture of sipuleucel-T activated APCs in both early and late disease states of prostate cancer, and generated similar T and B cell activation and cytokine production profiles consistent with immunological prime-boost. APC activation tended to be more robust in earlier disease states.