NY-ESO-1 antigen expression and immune response are associated with poor prognosis in MAGE-A4-vaccinated patients with esophageal or head/neck squamous cell carcinoma
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Shugo Ueda1, Yoshihiro Miyahara2, Yasuhiro Nagata3, Eiichi Sato4, Taizo Shiraishi5, Naozumi Harada6, Hiroaki Ikeda7, Hiroshi Shiku8 and Shinichi Kageyama9
1Department of Gastroenterological Surgery and Oncology, Kitano Hospital, Kita-ku, Osaka 530-8480, Japan
2Department of Personalized Cancer Immunotherapy, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
3Center for Comprehensive Community Care Education, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan
4Department of Pathology, Institute of Medical Science, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
5Department of Oncologic Pathology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
6United Immunity, Co., Ltd., Tsu, Mie 514-8507, Japan
7Department of Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan
8Departments of Immuno-Gene Therapy and Personalized Cancer Immunotherapy, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
9Department of Immuno-Gene Therapy, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
Shugo Ueda, email: [email protected]
Shinichi Kageyama, email: [email protected]
Keywords: cancer vaccine; MAGE-A4; NY-ESO-1; immune response; esophageal cancer
Received: July 27, 2018 Accepted: October 25, 2018 Published: November 13, 2018
MAGE-A4 antigen is a cancer-testis antigen that is frequently expressed in tumor tissues. 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 a CHP-MAGE-A4 vaccine. Twenty-two patients with advanced or metastatic cancer were enrolled, and were subcutaneously vaccinated with either 100 μg or 300 μg of CHP-MAGE-A4. Seven and 15 patients, respectively, were repeatedly vaccinated with 100 μg or 300 μg of CHP-MAGE-A4; patients in both groups received a median of 7 doses. No serious adverse events related to the vaccine were observed. Of 7 patients receiving the 100 μg dose, 2 (29%) showed immune responses, compared with 3 of the 14 (21%) patients who received the 300 μg dose. In total, MAGE-A4-specific antibody responses were induced in 5 of 21 (24%) patients. No differences in survival were seen between patients receiving the 100 μg and 300 μg doses, or between immune responders and non-responders. Eleven (50%) patients had pre-existing antibodies to NY-ESO-1. In 16 patients with esophageal or head/neck squamous cell carcinoma, the survival time was significantly shorter in those who had NY-ESO-1-co-expressing tumors. Patients with high pre-existing antibody responses to NY-ESO-1 displayed worse prognosis than those with no pre-existing response. Therefore, in planning clinical trials of MAGE-A4 vaccine, enrolling NY-ESO-1-expressing tumor or not would be a critical issue to be discussed. Combination vaccines of MAGE-A4 and NY-ESO-1 antigens would be one of the strategies to overcome the poor prognosis.
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