Dose-dependent effects of NY-ESO-1 protein vaccine complexed with cholesteryl pullulan (CHP-NY-ESO-1) on immune responses and survival benefits of esophageal cancer patients

Background: Cholesteryl pullulan (CHP) is a novel antigen delivery system for cancer vaccines. This study evaluated the safety, immune responses and clinical outcomes of patients who received the CHP-NY-ESO-1 complex vaccine, Drug code: IMF-001. Methods: Patients with advanced/metastatic esophageal cancer were enrolled and subcutaneously vaccinated with either 100 mu g or 200 mu g of NY-ESO-1 protein complexed with CHP. The primary endpoints were safety and humoral immune responses, and the secondary endpoint was clinical efficacy. Results: A total of 25 patients were enrolled. Thirteen and twelve patients were repeatedly vaccinated with 100 mu g or 200 mu g of CHP-NY-ESO-1 with a median of 8 or 9.5 doses, respectively. No serious adverse events related to the vaccine were observed. Three out of 13 patients in the 100-mu g cohort and 7 out of 12 patients in the 200-mu g cohort were positive for anti-NY-ESO-1 antibodies at baseline. In the 100-mu g cohort, an antibody response was observed in 5 out of 10 pre-antibody-negatives patients, and the antibody levels were augmented in 2 pre-antibody-positive patients after vaccination. In the 200-mu g cohort, all 5 pre-antibody-negative patients became seropositive, and the antibody level was amplified in all 7 pre-antibody-positive patients. No tumor shrinkage was observed. The patients who received 200 mu g of CHP-NY-ESO-1 survived longer than patients receiving 100 mu g of CHP-NY-ESO-1, even those who exhibited unresponsiveness to previous therapies or had higher tumor burdens. Conclusions: The safety and immunogenicity of CHP-NY-ESO-1 vaccine were confirmed. The 200 mu g dose more efficiently induced immune responses and suggested better survival benefits.