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T cell immunomonitoring and tumor responses in patients immunized with a complex of cholesterol-bearing hydrophobized pullulan (CHP) and NY-ESO-1 protein

Akiko Uenaka^1*, Hisashi Wada^2*, Midori Isobe¹, Takashi Saika³, Kazuhide Tsuji⁴, Eiichi Sato⁵, Shuichiro Sato¹, Yuji Noguchi¹, Ryohei Kawabata², Takushi Yasuda², Yuichiro Doki², Hiromi Kumon³, Keiji Iwatsuki⁴, Hiroshi Shiku⁶, Morito Monden², Achim A. Jungbluth⁷, Gerd Ritter⁷, Roger Murphy⁸, Eric Hoffman⁹, Lloyd J. Old⁷ and Eiichi Nakayama¹

¹Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

²Department of Surgery, Graduate School of Medicine, Osaka University, Suita, Japan

³Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

⁴Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

⁵Department of Pathology, Tokyo Medical University, Tokyo, Japan

⁶Department of Internal Medicine, Faculty of Medicine, Mie University, Tsu, Japan

⁷Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York, USA

⁸Ludwig Institute for Cancer Research, Austin and Repatriation Medical Center, Melbourne, Australia

⁹Ludwig Institute for Cancer Research, Office of Clinical Trials Management, New York, USA

Abstract

We recently showed that vaccination with a complex of cholesterol-bearing hydrophobized pullulan and NY-ESO-1 protein (CHP-NY-ESO-1) elicited antibody responses in 9 of 9 patients vaccinated in a clinical trial. In this study, we performed T cell immunomonitoring and analyzed tumor responses in these patients. To evaluate CD4 and CD8 T cell responses, an IFN-γ secretion assay was used. The assay showed low background and was sensitive for detecting antigen-specific T cells. An increase in the CD4 T cell response was observed in 2 of 2 initially sero-positive and 5 of 7 initially sero-negative patients after vaccination. An increase in the CD8 T cell response was also observed in 2 of 2 sero-positive and 5 of 7 sero-negative patients after vaccination. Analysis of peptides recognized by CD4 and CD8 T cells revealed two dominant NY-ESO-1 regions, 73-114 and 121-144. Tumor responses were observed in 3 esophageal cancer patients and a malignant melanoma patient. In 3 of 4 prostate cancer patients, prostate-specific antigen (PSA) values stabilized during the course of vaccination. The use of whole protein, containing multiple CD4 and CD8 epitopes, may be beneficial for cancer vaccines to prevent tumors from evading the immune response.