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Open Access 01-12-2013 | Research

Dose-dependent effects of NY-ESO-1 protein vaccine complexed with cholesteryl pullulan (CHP-NY-ESO-1) on immune responses and survival benefits of esophageal cancer patients

Authors: Shinichi Kageyama, Hisashi Wada, Kei Muro, Yasumasa Niwa, Shugo Ueda, Hiroshi Miyata, Shuji Takiguchi, Sahoko H Sugino, Yoshihiro Miyahara, Hiroaki Ikeda, Naoko Imai, Eiichi Sato, Tomomi Yamada, Masaharu Osako, Mami Ohnishi, Naozumi Harada, Tadashi Hishida, Yuichiro Doki, Hiroshi Shiku

Published in: Journal of Translational Medicine | Issue 1/2013

Abstract

Background

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 the CHP-NY-ESO-1 complex vaccine, Drug code: IMF-001.

Methods

Patients with advanced/metastatic esophageal cancer were enrolled and subcutaneously vaccinated with either 100 μg or 200 μg of NY-ESO-1 protein complexed with CHP. The primary endpoints were safety and humoral immune responses, and the secondary endpoint was clinical efficacy.

Results

A total of 25 patients were enrolled. Thirteen and twelve patients were repeatedly vaccinated with 100 μg or 200 μg of CHP-NY-ESO-1 with a median of 8 or 9.5 doses, respectively. No serious adverse events related to the vaccine were observed. Three out of 13 patients in the 100-μg cohort and 7 out of 12 patients in the 200-μg cohort were positive for anti-NY-ESO-1 antibodies at baseline. In the 100-μg cohort, an antibody response was observed in 5 out of 10 pre-antibody-negatives patients, and the antibody levels were augmented in 2 pre-antibody-positive patients after vaccination. In the 200-μg cohort, all 5 pre-antibody-negative patients became seropositive, and the antibody level was amplified in all 7 pre-antibody-positive patients. No tumor shrinkage was observed. The patients who received 200 μg of CHP-NY-ESO-1 survived longer than patients receiving 100 μg of CHP-NY-ESO-1, even those who exhibited unresponsiveness to previous therapies or had higher tumor burdens.

Conclusions

The safety and immunogenicity of CHP-NY-ESO-1 vaccine were confirmed. The 200 μg dose more efficiently induced immune responses and suggested better survival benefits. (Clinical trial registration number NCT01003808).

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Title: Dose-dependent effects of NY-ESO-1 protein vaccine complexed with cholesteryl pullulan (CHP-NY-ESO-1) on immune responses and survival benefits of esophageal cancer patients
Authors: Shinichi Kageyama
Hisashi Wada
Kei Muro
Yasumasa Niwa
Shugo Ueda
Hiroshi Miyata
Shuji Takiguchi
Sahoko H Sugino
Yoshihiro Miyahara
Hiroaki Ikeda
Naoko Imai
Eiichi Sato
Tomomi Yamada
Masaharu Osako
Mami Ohnishi
Naozumi Harada
Tadashi Hishida
Yuichiro Doki
Hiroshi Shiku
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Journal of Translational Medicine / Issue 1/2013
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/1479-5876-11-246

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