Development of immunotherapy for lung cancer utilizing p53 specific cytotoxic T lymphocytes
| Project/Area Number |
09671403
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | Aichi Cancer Center Research Institute |
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Principal Investigator |
MITSUDOMI Tetsuya Aichi Cancer Ctr., Res. Inst. Researcher, 研究所, 研究員 (70209807)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Toshitada Aichi Cancer Ctr., Res. Inst. Dep. Immunology, Chief, 免疫学部, 部長 (00124529)
TAKAHASHI Takashi Aichi Cancer Ctr., Res. Inst. Dep. Ultrastruct. Res., Chief, 超微形態学部, 部長 (50231395)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | p53 / CTL / lung cancer / MAGE3 / HLA / dendritic cell / autoantibody / ELISA / 免疫療法 / HLA-A24 / ペプチド / 抗体 |
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| Research Abstract |
1) Auto-antibodies against p53 protein in sera of NSCLC patients: We examined 188 consecutive patients with NSCLS for auto antibodies against p53 by enzyme-linked imunosorbent assay. p53 antibodies were detected in 34 patients of 188 (18%). Patients with squamous cell carcinoma or those with stage III-IV disease had a significantly higher incidence of p53 antibodies, respectively. Prevalence of p53 antibodies in patients with tumors having abnormal p53 protein accumulation was higher than that in patients without p53 abnormality (28% vs 14%). However, our data did not indicate clinical usefulness of p53 antibodies as a marker for relapse or prognosis of NSCLC.
2) Frequency of MAGE-3 gene expression in HLA-A2 positive patients with non-small cell lung cancer: Tumor cells expressing MAGE-3 are eliminated by cytotoxic T lymphocytes in HLA A1 and A2 restricted fashion. Therefore cancer patients whose tumor co-expresses HLA-A1 or -A2 and MAGE-3 can be potential candidates of vaccine therapy.
… More
Alternately, such tumors might have eliminated in vivo before becoming clinically overt tumor. We assessed the relationship between HLA-A1 or -A2 expression and MAGE-1 or -3 gene expression in 57 lung cancers. MAGE-3 were detected in 24 (42%). HLA-A2 was expressed in 17 (30%) at the protein level. The frequency of MAGE-3 expression in HLA-A2 patients was 5/17 (29%), somewhat lower than that of patients without HLA-A2 expression, 18/38 (47%) (p = 0.17). We conclude that there is no clear evidence for elimination of lung cancers co-expressing HLA-A2 and MAGE-3 in vivo. Approximately 10 percent (5/55) of Japanese lung cancer patients are potential candidates for MAGE-3 based immunotherapy.
3) Induction of HLA A24 restricted p53 specific CTL using dendritic cells(DC): Using 6 p53-derived peptides as antigens and DC derived from PBMC of healthy volunteers as APC, we tried to induce p53 specific CTL. However, none of the 6 peptide successfully induced CTL. Although we modified the method by using immature DC instead of mature DC, or by adding β2 microglobulin but in vain. Although there is a possibility that the selection of peptides itself was not appropriate, another possibility exists that precursor frequency of CTL was below the detection level since we solely used PBMC from healthy donors. Less
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Report
(4 results)
Research Products
(9 results)
