NY-ESO-1 is a prototypic cancer/testis antigen. In a recent phase I clinical trial, we vaccinated 13 patients bearing NY-ESO-1-expressing tumors with a complex of cholesterol-bearing hydrophobized pullulan (CHP) and NY-ESO-1 protein (CHP-NY-ESO-1) and showed efficient induction of NY-ESO-1 antibody, and CD4 and CD8 T cell responses using peripheral blood from the patients. In our study, we analyzed heteroclitic serological responses in those patients after vaccination. Serological response against 11 tumor antigens including MAGE-A1, MAGE-A3, MAGE-A4, CT7/MAGEC1, CT10/MAGEC2, CT45, CT46/HORMAD1, SOX2, SSX2, XAGE1B and p53 was examined by enzyme-linked immunosorbent assay (ELISA) using sera from ten vaccinated patients. Expression of tumor antigens was determined by reverse transcription-polymerase chain reaction or immunohistochemistry. Eight of nine patients who showed antibody responses against NY-ESO-1 also showed an antibody response against at least 1 of these 11 tumor antigens after vaccination. In one patient, seven tumor antigens were recognized. Specificity analysis of the antibody response by ELISA using control recombinant proteins and synthetic peptides and by Western blot showed that the response was not against His6-tag and/or bacterial products included in a preparation of CHP-NY-ESO-1 used for vaccination. Thus, heteroclitic serological responses appear to be indicative of the overall immune response against the tumor, and their analysis could be useful for immune monitoring in cancer vaccine.
cancer vaccine, pullulan, cancer testis antigen, heteroclitic antibody response, NY-ESO-1
NCBI PubMed ID: 21413013Publication DOI: 10.1002/ijc.26074Journal NLM ID: 42124Publisher: New York, NY: Wiley-Liss
Correspondence: hwada@gesurg.med.osaka-u.ac.jp
Institutions: Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan, Department of Respiratory Medicine, Kawasaki Medical School, Kurashiki, Japan, New York Branch at Memorial Sloan-Kettering Cancer Center, Ludwig Institute for Cancer Research, New York, USA, Department of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Osaka, Japan, Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan, Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan, Melbourne Centre for Clinical Sciences, Ludwig Institute for Cancer Research, Melbourne, Australia, Office of Clinical Trials Management, Ludwig Institute for Cancer Research, New York, USA, Faculty of Health and Welfare, Kawasaki University of Medical Welfare, Kurashiki, Japan
Methods: ELISA, Western blotting, biological assays, derivatization