| Project/Area Number |
16390468
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Kinki University |
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Principal Investigator |
UEMURA Hirotsugu Kinki University, School of Medicine, Professor, 医学部, 教授 (90213397)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Motoyoshi Kinki University, School of medicine, Assist.Prof., 医学部, 講師 (30347562)
HIRAO Yoshihiko Nara Med.Univ., School of Med., Professor, 医学部, 教授 (00133207)
YOSHIKAWA Kazuhiro Aichi Med.Univ., School of Med., Assist.Prof., 医学部, 講師 (60109759)
UEJIMA Shigeya Kinki University, Hospital, Associ.Prof., 医学部附属病院, 助教授 (60213336)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2004: ¥8,700,000 (Direct Cost: ¥8,700,000)
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| Keywords | renal cell carcinoma / CA9 (Carbonic Anhydrase 9) / peptide vaceine |
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| Research Abstract |
We have previously developed 3 CA9-derived peptide vaccines (CA9p219, p288, p323) having the ability to induce HLA-A2402 restricted CA9 specific CTL. Recently a phase-I peptide vaccination trial was carried out in 23 patients with cytokine refractory RCC patients, and resulted in promising efficacy without any major adverse events. However, more than 3 months were needed for induction of specific CTL and more than 6 months were needed for clinical responses. This may be due to relatively low immunogenic peptides. The aim of our study is to develop more immunogenic new peptide vaccines having the higher ability to induce CA9-specific CTL response. We made 25 kinds of CA9 9mer peptides including modified peptides of CA9p219 and CA9p288, and checked their affinity to HLA-A24 molecule by MHC stabilization assay. Surprisingly, CA9p219 had a low affinity although it has high affinity estimation by the computer software and actually had the highest ability of CTL induction in the clinical trial, indicating that real affinity is not associated with the affinity estimation. Based on these data, we screened all peptide made in this study whether these peptides could induce CA9 specific CTL responses. We found several peptides have the higher ability to induce CA9 specific CTL responses. We are currently investigating direct killing capability to CA9 positive cancer cells (SW620) of these peptides.
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