Takuro Saito1, Hisashi Wada2, Makoto Yamasaki1, Hiroshi Miyata1, Hiroyoshi Nishikawa3, Eiichi Sato4, Shinichi Kageyama5, Hiroshi Shiku5, Masaki Mori1, Yuichiro Doki1. 1. Department of Gastroenterological Surgery, Japan. 2. Department of Gastroenterological Surgery, Japan; Department of Clinical Research in Tumor Immunology, Graduate School of Medicine, Japan. Electronic address: hwada@gesurg.med.osaka-u.ac.jp. 3. Experimental Immunology, Immunology Frontier Research Center Osaka University, Suita, Osaka, Japan. 4. Department of Pathology, Tokyo Medical University, Tokyo, Japan. 5. Departments of Immuno-Gene Therapy and Cancer Vaccine, Mie University, Tsu, Mie, Japan.
Abstract
PURPOSE: We conducted a cancer vaccine clinical trial with MAGE-A4 protein. Safety, clinical response, and antigen-specific immune responses were analyzed and the prognostic factors by vaccination were investigated. EXPERIMENTAL DESIGN: Twenty patients with advanced esophageal, stomach or lung cancer were administered MAGE-A4 vaccine containing 300μg protein subcutaneously once every 2 weeks in six doses. Primary endpoints of this study were safety and MAGE-A4 immune responses. RESULTS: The vaccine was well tolerated. Fifteen of 20 patients completed one cycle of vaccination and two patients showed SD. A MAGE-A4-specific humoral immune response was observed in four patients who had high expression of MAGE-A4 and MHC class I on tumor cells. These four patients showed significantly longer overall survival than patients without an antibody response after vaccination (p=0.009). Patients with tumor cells expressing high MAGE-A4 or MHC class I antigen showed significantly longer overall survival than those with low expression. Induction of CD4 and CD8T cell responses was observed in three and six patients, respectively, and patients with induction of MAGE-A4-specific IFNγ-producing CD8T cells, but not CD4T cells, lived longer than those without induction. CONCLUSIONS: The CHP-MAGE-A4 vaccine was safe. Expression of MAGE-A4 and MHC class I in tumor tissue and the induction of a MAGE-A4-specific immune response after vaccination would be feasible prognostic markers for patients vaccinated with MAGE-A4.
PURPOSE: We conducted a cancer vaccine clinical trial with MAGE-A4 protein. Safety, clinical response, and antigen-specific immune responses were analyzed and the prognostic factors by vaccination were investigated. EXPERIMENTAL DESIGN: Twenty patients with advanced esophageal, stomach or lung cancer were administered MAGE-A4 vaccine containing 300μg protein subcutaneously once every 2 weeks in six doses. Primary endpoints of this study were safety and MAGE-A4 immune responses. RESULTS: The vaccine was well tolerated. Fifteen of 20 patients completed one cycle of vaccination and two patients showed SD. A MAGE-A4-specific humoral immune response was observed in four patients who had high expression of MAGE-A4 and MHC class I on tumor cells. These four patients showed significantly longer overall survival than patients without an antibody response after vaccination (p=0.009). Patients with tumor cells expressing high MAGE-A4 or MHC class I antigen showed significantly longer overall survival than those with low expression. Induction of CD4 and CD8T cell responses was observed in three and six patients, respectively, and patients with induction of MAGE-A4-specific IFNγ-producing CD8T cells, but not CD4T cells, lived longer than those without induction. CONCLUSIONS: The CHP-MAGE-A4 vaccine was safe. Expression of MAGE-A4 and MHC class I in tumor tissue and the induction of a MAGE-A4-specific immune response after vaccination would be feasible prognostic markers for patients vaccinated with MAGE-A4.