T cell immunomonitoring and tumor responses in patients immunized with a complex of cholesterol-bearing hydrophobized pullulan (CHP) and NY-ESO-1 protein.
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-gamma 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.
Uenaka
Akiko
A
Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Shikata-cho, Okayama, Japan.
Wada
Hisashi
H
Isobe
Midori
M
Saika
Takashi
T
Tsuji
Kazuhide
K
Sato
Eiichi
E
Sato
Shuichiro
S
Noguchi
Yuji
Y
Kawabata
Ryohei
R
Yasuda
Takushi
T
Doki
Yuichiro
Y
Kumon
Hiromi
H
Iwatsuki
Keiji
K
Shiku
Hiroshi
H
Monden
Morito
M
Jungbluth
Achim A
AA
Ritter
Gerd
G
Murphy
Roger
R
Hoffman
Eric
E
Old
Lloyd J
LJ
Nakayama
Eiichi
E
D000368:Aged; D000917:Antibody Formation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D002784:Cholesterol / Q000008:administration & dosage* / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000009:adverse effects; D005260:Female; D005936:Glucans / Q000008:administration & dosage* / Q000494:pharmacology; D015234:HLA-A Antigens / Q000276:immunology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology*; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D010455:Peptides / Q000276:immunology; D014611:Vaccination
D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D005936:Glucans; D015234:HLA-A Antigens; D008565:Membrane Proteins; D010455:Peptides; D007371:Interferon-gamma; C009109:pullulan; D002784:Cholesterol