2005 Fiscal Year Final Research Report Summary
Analysis of human tumor immunity using a new model system with endometrial cancer transplanted SCID mice for clinical application
| Project/Area Number |
16591686
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Obstetrics and gynecology
|
|---|
| Research Institution | Keio University |
|---|
Principal Investigator |
TSUKAMOTO Makoto Keio University, School of medicine, Instructor, 医学部, 助手 (50365441)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KAWAKAMI Yutaka Keio University, School of medicine, Professor, 医学部, 教授 (50161287)
AOKI Daisuke Keio University, School of medicine, Professor, 医学部, 教授 (30167788)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Keywords | endometrial cancer / MSI / tumor antigen / SCID mouse / Immunodeficiency |
|---|
| Research Abstract |
We have developed the new mouse model system in which we are able to observe tumor invasion T cells in the tumor and the spleen as well as a tumor specific human IgG antibody upon transplantation of human tumor tissue into the immune deficiency mouse. In this study, we analyzed the immune responses to the mutated proteins by the microsatellite stability (MSI) which was particularly high in endometrial cancer. The immune response the PTEN frameshift mutation, often observed in MSI-positive endometrial cancers, and the identification of endometrial cancer antigens by SEREX using sera from MSI-positive patients and from MSI-positive tissue transplanted immune deficiency mice were studied. To detect IgG antibody to the frameshift mutated PTEN which was frequently found in endometrial cancer, the full length protein and the frameshift mutated proteins EX7(A4) and EX8(A5) for PTEN were constructed. The antibody for the frameshift mutated protein (EX8) by MSI was detected in a endometrial cancer patient with the EX8 mutation. Cancer-testis antigen SCP-1 and KIAA0445 were identified by SEREX with 3 sera samples from MSI-positive endometrial cancer patients. We performed 3 SEREX experiments using serum from MSI-positive endometrial cancer transplanted immune deficient mice and isolated 18 genes. With previous models, immune responses against 5 of the isolated genes were not detected in patients' sera, so the new model, in which we used sera with the tumor transplanted immune deficiency mice, was effective for the identification of tumor antigens. In 14 of the 18 identified genes, other potential frameshift mutations in the proteins may lead to further targets for immune therapy in future.
|
