Analysis of peripheral and local anti-tumor immune response in esophageal cancer patients after NY-ESO-1 protein vaccination.
NY-ESO-1 antigen is a prototype of a class of cancer/testis antigens. We carried out a clinical trial using NY-ESO-1 whole protein as a cancer vaccine for 13 advanced cancer patients. We have recently reported that vaccine elicited humoral and cellular immune responses in 9 cancer patients including 4 esophageal cancer patients, and clinical responses were also observed in 4 of 5 evaluable patients. In this study, we analyzed the responses in 8 esophageal cancer patients including 4 newly enrolled patients. Patients were injected subcutaneously at biweekly intervals with NY-ESO-1 recombinant protein formulated with cholesterol-bearing hydrophobized pullulan. Induction of antibody, and CD4 and CD8 T-cell responses were observed in 7, 7 and 6 patients, respectively, out of 8 patients. 1 PR, 2 SD and 2 mixed clinical responses were observed in 6 evaluable patients. No significant adverse events were observed. Furthermore, we analyzed NY-ESO-1 and MHC class I expression and the infiltration of immune cells into tumor samples obtained before and after vaccination from 4 patients by immunohistochemistry. The results showed 2 patients with disappearance of CD4 and CD8 T-cell infiltration, 1 patient with increase in the number of CD68(+) macrophages and 1 patient with tumor antigen loss in the progressive tumors following vaccinations. The induction of NY-ESO-1 immunity and some preferable clinical outcomes were observed in esophageal cancer patients by vaccination with NY-ESO-1. However, the tumors grew eventually by various mechanisms after vaccination.
Wada
Hisashi
H
Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan. hwada@gesurg.med.osaka-u.ac.jp
Sato
Eiichi
E
Uenaka
Akiko
A
Isobe
Midori
M
Kawabata
Ryohei
R
Nakamura
Yurika
Y
Iwae
Shigemichi
S
Yonezawa
Kouichiro
K
Yamasaki
Makoto
M
Miyata
Hiroshi
H
Doki
Yuichiro
Y
Shiku
Hiroshi
H
Jungbluth
Achim A
AA
Ritter
Gerd
G
Murphy
Roger
R
Hoffman
Eric W
EW
Old
Lloyd J
LJ
Monden
Morito
M
Nakayama
Eiichi
E
D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D004938:Esophageal Neoplasms / Q000276:immunology* / Q000628:therapy; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000276:immunology*; D008875:Middle Aged
D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D008565:Membrane Proteins