Abstract A029: Cell-based cancer immunotherapy using tumor presenting cells: A phase II trial with local advance prostate cancer patients

Abstract

We described a non-randomized control phase II trial, using a novel Cell Based Cancer Immunotherapy using Tumor Presenting Cells (TPC). The patient population was selected at HCPA – Porto Alegre Brazil (University Hospital). Patients with clinical localized prostate cancer and scheduled to undergo radical retro pubic prostatectomy (RRP) were identified. High-risk patients (initial PSA levels above 10 ng/ml, Gleason above 8 or upstaged from the clinical staging) were offer to participate on the trial. This group of patients represent a very important clinical population that cloud benefit from an adjuvant therapy. Tumor Presenting Cells are a new strategy for immunotherapy. Solid tumor cells as other non-immunological cells do not present MHC Class II. The MHC class II is a critical molecule responsible for peptide presentation to T helper cells. The presence of a not-self peptide on a MHC II molecule trigger the production of cytokines responsible for different steps on T cell expansion and maturation. Without the appropriate cytokine stimulation, cytotoxic T cells that identified a not-self peptide associate to a MHC class I molecules, may not proliferate or even be induce to anergy. In our model, solid tumor cells (prostate cancer) are induce to express MHCII on their surface. In this novel approach of Cell Based Cancer Immunotherapy (CBCI), patient's tumor cells were expanded in tissue culture and treated causing de novo expression of MHC II and activation of the MHC II peptide presentation pathway. Thus, the modified cancer cells are bifunctional, being capable of activating both helper T cells (MHC II) and cytotoxic T cells (MHCI), leading to cytokine production and a surprisingly robust and cancer-specific immune response. The modified solid tumor cell by itself will now behave as an antigen-presenting cell creating a Tumor Presenting Cell (TPC). Once the tumor cells are modified, they are irradiated and inoculated as intradermal injections (7 doses). Although the individualized preparation of CBCI is labor intensive, we were able to prepare the cell material on almost all collected samples (103/107 - 96%). DTH reactions (≥ 5 mm) were positive in 73% of the patients (16/23). This study corroborates with low toxicity of cell based immunotherapy. We have found mild skin reactions on inoculation sites in all vaccinated patients. More intense reactions (ulceration, low-grade fever, and adenopathy) were found in 13% of patients (3/23). We demonstrated a clinical benefit with the used of the CBCI: 27% (6/22) of the patients submitted to CBCI presented detectable levels of PSA (above 0.004 ng/mL) after 5 years, when compare to 53% (19/36) on the control group (p=0.03). There was also trend on reduction of cancer related mortality, 4% (1/23) on the CBCI group against 10% (4/40) on the control group. Several new therapies were approved in recent years for advanced prostate cancer treatment. The pharmaco-economic cost of these therapies are significant, and most of them shown an improvement survival of less than six months. New therapies such as Cell Base Cancer Immunotherapy with Tumor Presenting Cells could change this scenario, improving quality life, reducing mortality and cost to the health care providers. We are now designing a Phase III trial in North America for local advance prostate cancer. Other indication (triple negative breast cancer, pancreatic or gastric cancer patients) are also under evaluation.

Citation Format: Fernando T. Kreutz. Cell-based cancer immunotherapy using tumor presenting cells: A phase II trial with local advance prostate cancer patients. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr A029.