Antibody response against NY-ESO-1 in CHP-NY-ESO-1 vaccinated patients
Ryohei Kawabata, Hisashi Wada, Midori Isobe, Takashi Saika, Shuichiro Sato, Akiko Uenaka, Hiroshi Miyata, Takushi Yasuda, Yuichiro Doki, Yuji Noguchi, Hiromi Kumon, Kazuhide Tsuji, Keiji Iwatsuki, Hiroshi Shiku, Gerd Ritter, Roger Murphy, Eric Hoffman, Lloyd J Old, Morito Monden, Eiichi Nakayama, Ryohei Kawabata, Hisashi Wada, Midori Isobe, Takashi Saika, Shuichiro Sato, Akiko Uenaka, Hiroshi Miyata, Takushi Yasuda, Yuichiro Doki, Yuji Noguchi, Hiromi Kumon, Kazuhide Tsuji, Keiji Iwatsuki, Hiroshi Shiku, Gerd Ritter, Roger Murphy, Eric Hoffman, Lloyd J Old, Morito Monden, Eiichi Nakayama
Abstract
NY-ESO-1 specific humoral responses are frequently observed in patients with various types of NY-ESO-1 antigen expressing tumors. In a large proportion of NY-ESO-1 antibody-positive patients of NY-ESO-1-specific CD8 T-cells can also be detected suggesting that monitoring of the NY-ESO-1 specific humoral immune response may be a relevant and more practical surrogate for estimating the overall immune response against NY-ESO-1 in clinical vaccine studies. We have immunized 9 cancer patients with full length NY-ESO-1 protein formulated with cholesterol-bearing hydrophobized pullulan (CHP-NY-ESO-1) and investigated the humoral immune responses against NY-ESO-1. Seven patients were NY-ESO-1 antibody-negative and 2 patients were positive prior to vaccination. Vaccination with CHP-NY-ESO-1 resulted in the induction or increase of NY-ESO-1 antibody responses in all 9 patients immunized. Epitope analysis revealed 5 regions in the NY-ESO-1 protein molecule that were recognized by antibodies induced after vaccination. The 5 regions were also recognized by antibodies present in nonvaccinated, NY-ESO-1 antibody-positive cancer patients. A peptide spanning amino acids 91-108 was recognized in 6 out of 9 vaccinated patients and in 8 out of 9 nonvaccinated, sero-positive patients, being the most dominant antigenic epitope in NY-ESO-1 for antibody recognition in cancer patients. In conclusion, we showed that CHP-NY-ESO-1 protein vaccination had a potent activity for inducing humoral immune responses against NY-ESO-1 antigen in cancer patients. The antigenic epitopes recognized by antibodies in the vaccinated patients were similar to those recognized in cancer patients with spontaneous humoral immunity against NY-ESO-1.
(c) 2007 Wiley-Liss, Inc.
Source: PubMed