Abstract A16: A phase I/II clinical trial of a MUC1-glycopeptide dendritic cell vaccine in castrate resistant non-metastatic prostate cancer patients

Background: Current treatment options for prostate cancer (PCa) patients with rising PSA despite castrate testosterone levels are limited. A number of immunotherapeutic approaches for the treatment of PCa have been studied with varying efficacy. MUC1 has been an antigen of interest for immunotherapy, however, tolerance to the peptide epitopes has led to limited immune response. A glycosylated version of the antigen, Tn-100mer-MUC1, was shown to be effective in overcoming tolerance in pre-clinical studies. Dendritic cells (DC) take up and process Tn-100mer-MUC1 and present both glycopeptide and peptide epitopes. We report the results of a phase I/II clinical trial of an autologous DC vaccine loaded with Tn-100mer-MUC1 and KLH in patients with castrate resistant, non-metastatic PCa. Methodology: Eight consenting patients with rising PSA were enrolled into the study; however one patient progressed with bone metastases before receiving the first vaccine dose. To generate the autologous DC vaccine, patient's monocytes were elutriated from apheresis product and cultured under conditions suitable for the generation of mature and motile DCs. Tn-100mer-MUC1 glycopeptide and clinical-grade KLH, as a control antigen, were loaded onto the DCs. The final vaccine product consisting of Tn-100mer-MUC1 and KLH loaded DCs mixed 10:1 was cryopreserved and tested before release and administration to patients. Patients were treated with 3 vaccine injections every two weeks administered intradermally (i.d.) and intranodally (i.n.) to a single inguinal node for the first dose only. Booster i.d. vaccinations were given 6 and 12 months following the first dose in patients showing stable disease. Each dose consisted of the administration of a total of 1.2 × 107 DCs. Toxicity and biologic effects of the vaccine were evaluated by physical, imaging and clinical chemistry examinations at regular intervals. PSA doubling times were determined using the Memorial Sloan-Kettering Cancer Center PSA doubling time calculator. Results: The vaccine was safe; there were no serious vaccine-related adverse events. Toxicity was limited to grade 1 and 2 injection site reactions. Four of 7 patients treated were withdrawn after 6 months because of radiologic progression or elevated PSA. Three patients showed stable disease and received all five vaccinations. Our primary endpoint, reduction in PSA, was not achieved. However, the rate of PSA rise decreased in 6 of 7 patients. Overall the PSA doubling tim