Identification of human papillomavirus 16-E6 protein-derived peptides with the potential to generate cytotoxic T-lymphocytes toward human leukocyte antigen-A24+ cervical cancer.
Human papillomavirus 16 (HPV16)-E6 and -E7 proteins are considered to be appropriate targets in specific immunotherapy for cervical cancer. In this study, we attempted to identify epitope peptides from the HPV16-E6 protein that have the potential to generate cytotoxic T-lymphocytes (CTLs) toward human leukocyte antigen (HLA)-A24+ cervical cancer. Two HPV16-E6 peptides at positions 75-83 and 91-100 effectively induced peptide-specific CTLs from peripheral blood mononuclear cells of HLA-A24+ cervical cancer patients. These HPV16-E6 peptide-induced CTLs showed cytotoxicity against HLA-A24+ and HPV16-E6 protein-expressing cervical cancer cells. Experiments with blocking antibodies and cold inhibition targets revealed that the cytotoxicity was mainly dependent on peptide-specific and CD8+ T cells. In addition, based on our observation that induction of immunoglobulin G (IgG) reactive to administered CTL-directed peptides is correlated with clinical responses, we attempted to detect IgG reactive to HPV16-E6 peptides in the plasma of cancer patients. As a result, IgGs reactive to the HPV16-E691-100 peptide were detected in 4 of 12 cervical cancer patients. These results indicate that these HPV16-E6-derived peptides are good candidates in peptide-based immunotherapy for HLA-A24+ cervical cancer patients.
Hara
Miho
M
Department of Immunology, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.
Matsueda
Satoko
S
Tamura
Mayumi
M
Takedatsu
Hiroko
H
Tanaka
Masahiro
M
Kawano
Kouichiro
K
Mochizuki
Kazuo
K
Kamura
Toshiharu
T
Itoh
Kyogo
K
Harada
Mamoru
M
D005260:Female; D015234:HLA-A Antigens / Q000276:immunology; D059871:HLA-A24 Antigen; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007167:Immunotherapy / Q000379:methods; D009000:Monocytes; D009856:Oncogene Proteins, Viral / Q000502:physiology*; D027383:Papillomaviridae / Q000472:pathogenicity; D012097:Repressor Proteins / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000821:virology*
C068651:E6 protein, Human papillomavirus type 16; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D007074:Immunoglobulin G; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins