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, Hisashi Wada, Midori Isobe, Takashi Saika, Kazuhide Tsuji, Eiichi Sato, Shuichiro Sato, Yuji Noguchi, Ryohei Kawabata, Takushi Yasuda, Yuichiro Doki, Hiromi Kumon, Keiji Iwatsuki, Hiroshi Shiku, Morito Monden, Achim A. Jungbluth, Gerd Ritter, Roger Murphy, Eric Hoffman, Lloyd J. OldEiichi Nakayama

Research output: Contribution to journalArticle

88 Citations (Scopus)

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.

Original languageEnglish
JournalCancer Immunity
Volume7
Publication statusPublished - Apr 19 2007

    Fingerprint

Keywords

  • CHP-NY-ESO-1
  • Cancer vaccine
  • Cellular immunity
  • Human
  • Immunohistochemistry

ASJC Scopus subject areas

  • Immunology
  • Cancer Research

Cite this

Uenaka, A., Wada, H., Isobe, M., Saika, T., Tsuji, K., Sato, E., Sato, S., Noguchi, Y., Kawabata, R., Yasuda, T., Doki, Y., Kumon, H., Iwatsuki, K., Shiku, H., Monden, M., Jungbluth, A. A., Ritter, G., Murphy, R., Hoffman, E., ... Nakayama, E. (2007). T cell immunomonitoring and tumor responses in patients immunized with a complex of cholesterol-bearing hydrophobized pullulan (CHP) and NY-ESO-1 protein. Cancer Immunity, 7.