Identification of a gene coding for a new squamous cell carcinoma antigen recognized by the CTL

被引:118
作者
Nakao, M
Shichijo, S
Imaizumi, T
Inoue, Y
Matsunaga, K
Yamada, A
Kikuchi, M
Tsuda, N
Ohta, K
Takamori, S
Yamana, H
Fujita, H
Itoh, K
机构
[1] Kurume Univ, Sch Med, Dept Immunol, Fukuoka 8300011, Japan
[2] Kurume Univ, Sch Med, Dept Surg, Fukuoka 8300011, Japan
[3] Kurume Univ, Sch Med, Dept Anat 2, Fukuoka 8300011, Japan
[4] Kurume Univ, Res Ctr Innovat Canc Therapy, Canc Vaccine Dev Div, Fukuoka, Japan
关键词
D O I
10.4049/jimmunol.164.5.2565
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Peptide-based specific immunotherapy has resulted in tumor regression in some melanoma patients. However, tumor Ags and peptides for specific immunotherapy, except for treatment of melanomas, have not yet been well identified. In this study, we report a gene encoding a new squamous cell carcinoma (SCC) Ag recognized by cells of the HLA-A24-restricted and tumor-specific CTL line. This gene with 3958-bp length was transcribed from the chromosome 6q22 with six exons, and its mRNA was ubiquitously expressed in both SCCs and normal tissues, and partly expressed in adenocarcinomas. The deduced 958-aa sequence encoded by this gene showed no similarity to any known amino acid sequences. This gene product had a characteristic of an endoplasmic reticulum-resident protein. A 100-kDa protein was detected in the vast majority of SCCs from various tissues, in majority of renal cell carcinomas and brain tumors, and in about one-third of melanomas and adenocarcinomas from various organs other than the breast. In contrast, it was not expressed at all in any of the normal cells or tissues tested, including the testis and fetal liver. Three different peptides at positions 93-101, 161-169, and 899-907 of this Ag were recognized by this CTL line, and all of them induced HLA-A24-restricted and tumor-specific CTLs from PBMCs of SCC patients. Therefore, these peptides may be useful for peptide-based specific immunotherapy of HLA-A24(+) patients with SCC in various organs, as well as for treatment of other cancer.
引用
收藏
页码:2565 / 2574
页数:10
相关论文
共 50 条
[11]  
2-I
[12]  
Imaizumi T, 1999, INT J CANCER, V83, P760, DOI 10.1002/(SICI)1097-0215(19991210)83:6<760::AID-IJC11>3.0.CO
[13]  
2-R
[14]  
Imanishi T., 1992, HLA 1991, P1065
[15]   Simultaneous humoral and cellular immune response against cancer-testis antigen NY-ESO-1:: Definition of human histocompatibility leukocyte antigen (HLA)-A2-binding peptide epitopes [J].
Jäger, E ;
Chen, YT ;
Drijfhout, JW ;
Karbach, J ;
Ringhoffer, M ;
Jäger, D ;
Arand, M ;
Wada, H ;
Noguchi, Y ;
Stockert, E ;
Old, LJ ;
Knuth, A .
JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 187 (02) :265-270
[16]  
KANG XQ, 1995, J IMMUNOL, V155, P1343
[17]   IDENTIFICATION OF THE IMMUNODOMINANT PEPTIDES OF THE MART-1 HUMAN-MELANOMA ANTIGEN RECOGNIZED BY THE MAJORITY OF HLA-A2-RESTRICTED TUMOR-INFILTRATING LYMPHOCYTES [J].
KAWAKAMI, Y ;
ELIYAHU, S ;
SAKAGUCHI, K ;
ROBBINS, PF ;
RIVOLTINI, L ;
YANNELLI, JR ;
APPELLA, E ;
ROSENBERG, SA .
JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 180 (01) :347-352
[18]   T-cell recognition of self peptides as tumor rejection antigens [J].
Kawakami, Y ;
Rosenberg, SA .
IMMUNOLOGIC RESEARCH, 1996, 15 (03) :179-190
[19]  
KAWAKAMI Y, 1995, J IMMUNOL, V154, P3961
[20]  
Kawamoto M, 1999, INT J CANCER, V80, P64, DOI 10.1002/(SICI)1097-0215(19990105)80:1<64::AID-IJC13>3.3.CO