2004 Fiscal Year Final Research Report Summary
Establishment of tumor specific immunotherapy for lung cancer patients ; Identification of tumor antigens and analysis of immune responses.
| Project/Area Number |
14370420
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Thoracic surgery
|
|---|
| Research Institution | University of Occupational and Environmental Health, Japan |
|---|
Principal Investigator |
YASUMOTO Kosei University of Occupational and Environmental Health Japan, School of Medicine, Professor, 医学部, 教授 (30150452)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SUGIO Kenji University of Occupational and Environmental Health, Japan, School of Medicine, Associate Professor, 医学部, 助教授 (70235927)
HANAGIRI Takeshi University of Occupational and Environmental Health, Japan, School of Medicine, Assistant Professor, 医学部, 講師 (30299614)
SUGAYA Masakazu University of Occupational and Environmental Health, Japan, School of Medicine, Research Associate, 医学部, 助手 (40352306)
|
|---|
| Project Period (FY) |
2002 – 2004
|
| Keywords | Lung cancer / tumor antigen / peptide / CTL / SEREX / immunotherapy / vaccine / antibody |
|---|
| Research Abstract |
It is very important to analyze tumor-specific immune responses in cancer patients for development of effective tumor specific immunotherapy. We have established 21 lung cancer cell lines and induced tumor-specific cytotoxic T lymphocytes (CTL) from regional lymph node lymphocytes in lung cancer patients. Several tumor associate antigens recognized by these CTLs were identified by cDNA expression cloning method. CTL Clone 1 and Clone 2 recognized autologous large cell carcinoma (A904L), whereas they did not respond to autologous EBV-B and PHA-blastoid T cells. Clone 1 recognized the tumor antigen restricted by HLA-A24. The antigen coding gene revealed a splicing variant of known gene. On the other hand, Clone 2 recognized the tumor antigen in the context of HLA-Cw7. The antigen coding gene was a function-unknown gene. The tumor specific CTL clone H1 against adenocarcinoma cell line (F1121L) was induced from regional lymph node lymphocytes. This CTL clone lysed autologous tumor cells in
… More
the context of HLA-B^*1507. The antigen recognized by the CTL was a new cancer/testis antigen. Identification of these lung cancer associated antigen facilitates peptide based specific immunotherapy for lung cancer patients.
In order to investigate the potential role of tumor-infiltrating B cells (TIB) in lung cancer, we demonstrated that humoral immune responses of TIB in lung cancer patients could be detected in SLID mice xenotransplanted model. By serological analysis of recombinant cDNA expression libraries (SERER), 25 distinct antigens reactive with IgG derived from TIB were identified in two lung cancer cell lines. Sequencing analysis showed that the functions of 14 antigens were known, and the function of other 11 genes were unknown. Furthermore, 4 out of the identified genes had extra-cellular region. These findings suggested that TIB-derived IgG played an important role in humoral immune response against lung cancer. The identified cancer related antigens may have a potential target for cancer vaccines and monoclonal antibody-based immunotherapies. Less
|
