Safety, efficacy, and immunogenicity of autologous tumor lysate-pulsed dendritic cell vaccination therapy after resection of stage IIA (T2N0, T3N0) esophageal cancer: A phase I trial.

Abstract

153 Background: Immunotherapy using active immunization of tumor associated antigens has been expected to improve the prognosis of malignant tumor patients. We conducted a phase I trial to investigate safety and efficacy of autologous tumor lysate-pulsed dendritic cell (DC) vaccination therapy after resection for esophageal cancer. Methods: Patients (pts) with stage IIA (T2N0 or T3N0, UICC TNM classification 6th edition) esophageal cancer after curative (R0) resection, ECOG PS 0-2, 20 years or more and adequate organ function were eligible. We used tumor lysate for DC vaccines; the lysates potentially contain mutated proteins or neoantigens derived from somatic mutations in each patient's tumor. Patients received DC vaccines (more than 5.0×106 cells) 6 times every 2 weeks. Primary endpoint was safety and secondary endpoint were efficacy including recurrence rate and immunological responses. Results: A total of 11 pts (median age: 71 years) were enrolled until the trial stopped on March 31, 2016, because standard of therapy for objective patients had changed. No treatment related adverse events of grade 3 or 4 were reported. Recurrence rate within 2 years were 18% (n=2). We performed whole-exome sequence of tumors and adjacent normal tissues with 5 pts, and identified mutated peptide derived from their tumor specific missense mutations. To examine immune responses against those predicted candidate neoepitopes, we immunized HLA-A2 transgenic mice (HHD-II mice) with the synthesized peptides from the 2 pts harboring HLA-A2. Conclusions: This study showed that autologous tumor lysate-pulsed DC vaccination therapy is safe and have expectation of recurrence risk reduction after resection of T2N0 or T3N0 esophageal cancer. Clinical trial information: UMIN000002837.