RESUMO
The aim of this study was to determine the efficacy and the biomarkers of the CHP-NY-ESO-1 vaccine complexed with full-length NY-ESO-1 protein and a cholesteryl pullulan (CHP) in patients with esophageal squamous cell carcinoma (ESCC) after surgery. We conducted a randomized phase II trial. Fifty-four patients with NY-ESO-1-expressing ESCC who underwent radical surgery following cisplatin/5-fluorouracil-based neoadjuvant chemotherapy were assigned to receive either CHP-NY-ESO-1 vaccination or observation as control. Six doses of CHP-NY-ESO-1 were administered subcutaneously once every two weeks, followed by nine more doses once every four weeks. The endpoints were disease-free survival (DFS) and safety. Exploratory analysis of tumor tissues using gene-expression profiles was also performed to seek the biomarker. As there were no serious adverse events in 27 vaccinated patients, we verified the safety of the vaccine. DFS in 2 years were 56.0% and 58.3% in the vaccine arm and in the control, respectively. Twenty-four of 25 patients showed NY-ESO-1-specific IgG responses after vaccination. Analysis of intra-cohort correlations among vaccinated patients revealed that 5% or greater expression of NY-ESO-1 was a favorable factor. Comprehensive analysis of gene expression profiles revealed that the expression of the gene encoding polymeric immunoglobulin receptor (PIGR) in tumors had a significantly favorable impact on outcomes in the vaccinated cohort. The high PIGR-expressing tumors that had higher NY-ESO-1-specific IgA response tended to have favorable prognosis. These results suggest that PIGR would play a major role in tumor immunity in an antigen-specific manner during NY-ESO-1 vaccinations. The IgA response may be relevant.
Assuntos
Vacinas Anticâncer , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Receptores de Imunoglobulina Polimérica , Anticorpos Antineoplásicos , Antígenos de Neoplasias , Cisplatino , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Fluoruracila , Glucanos , Humanos , Imunoglobulina A , Imunoglobulina G , Proteínas de Membrana , PrognósticoRESUMO
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 µg or 200 µg 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 µg or 200 µg 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-µg cohort and 7 out of 12 patients in the 200-µg cohort were positive for anti-NY-ESO-1 antibodies at baseline. In the 100-µg 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-µg 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 µg of CHP-NY-ESO-1 survived longer than patients receiving 100 µg 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 µg dose more efficiently induced immune responses and suggested better survival benefits. (Clinical trial registration number NCT01003808).