2006 Fiscal Year Final Research Report Summary
Development and clinical application of new anti-cancer drugs for oncoprotein CD98 as a molecular target.
| Project/Area Number |
17590467
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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 |
Applied pharmacology
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| Research Institution | University of Shizuoka |
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Principal Investigator |
ITOH Kunihiko Univ. Shizuoka, Sch. Pharm. Sci., Professor, 薬学部, 教授 (90221770)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Toshio Akita Univ., Sch. Med., Professor, 医学部, 教授 (20108559)
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| Project Period (FY) |
2005 – 2006
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| Keywords | CD98 / Monoclonal antibody / Phage display / Epitope peptide / Molecular targeting drugs |
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| Research Abstract |
Anti-CD98 monoclonal antibody, HBJ127 shows growth inhibition in vitro. Since elevated expression of CD98 is detected in tumor tissues, especially in squamous cell carcinomas, anti-tumor immunity may be inducible in the host by active immunization of peptides derived from epitope recognized by HBJ127. In this study, we identified HBJ127 epitope using phage display random peptide library and characterized the serum from epitope peptide-immunized mice. We identified the peptide sequence corresponding to the 442-444 (AFS) of human CD98 heavy chain (h. c. ) among isolated HBJ127-reactive peptide sequences. It was found that 413F is human specific amino acid. We estimated that this motif is HBJ127 epitope, since 1) HBJ127 reacts only with human species, and 2) HBJ127 epitope position is predicted in 418-529 of human CD98 h. c. Next, we prepared several epitope peptide-keyhole limpet hemocyanine (KLH) conjugates and immunized with BALB/c mice. The immune serum reacted with epitope peptide-KLH in a concentration dependent manner. They also reacted with epitope peptide-bovine serum albumin (BSA). From these results, the immune response occurred not only against the carrier protein but also against hapten (epitope peptide). The immune serum also reacted with recombinant human CD98 h. c. in a concentration dependent manner. These results suggest that CD98-reactive antibody repertoire can be inducible in the hosts by immunization of epitope peptide derived from HBJ127. This may indicate the usefulness of tumor suppressive antibody-derived epitope peptide immunization for induction of anti-tumor immunity.
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