지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2012.8
- 수록면
- 155 - 164 (10page)
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It is well established that blocking the interaction of EGFR with growth factors leads to the arrest of tumor growth, resulting in tumor cell death. ER414 is a human monoclonal antibody (mAb) derived by guided selection of the mouse mAb A13. The ER414 exhibited a ~17-fold lower affinity and, as a result, lower efficacy of inhibition of the EGF-mediated tyrosine phosphorylation of EGFR when compared with mAb A13 and cetuximab. We performed a stepwise in vitro affinity maturation to improve the affinity of ER414. We obtained a 3D model of ER414 to identify the amino acids in the CDRs that needed to be mutated. Clones were selected from the phage library with randomized amino acids in the CDRs and substitution of amino acids in the HCDR3 and LCDR1 of ER414 led to improved affinity. A clone, H3-14, with a ~20-fold increased affinity, was selected from the HCDR3 randomized library. Then three clones, ER2, ER78 and ER79, were selected from the LCDR1 randomized library based on the H3-14 but did not show further increased affinities compared to that of H3-14. Of the three, ER2 was chosen for further characterization due to its better expression than others. We successfully performed affinity maturation of ER414 and obtained antibodies with a similar affinity as cetuximab. And antibody from an affinity maturation inhibits the EGF-mediated tyrosine phosphorylation of EGFR in a manner similar to cetuximab.
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참고문헌 (29)
참고문헌 신청
Carpenter, G. / 1987 / Receptors for epidermal growth factor and other polypeptide mitogens / Annu. Rev. Biochem 56:881~914
Yarden, Y. / 2001 / Untangling the ErbB signalling network / Nat. Rev. Mol. Cell Biol 2:127~137
Laskin, J. J. / 2004 / Epidermal growth factor receptor: a promising target in solid tumours / Cancer Treat. Rev 30:1~17
Herbst, R. S. / 2002 / Monoclonal antibodies to target epidermal growth factor receptor-positive tumors: a new paradigm for cancer therapy / Cancer 94:1593~1611
Capdevila, J. / 2009 / Anti-epidermal growth factor receptor monoclonal antibodies in cancer treatment / Cancer Treat. Rev 35:354~363
Yarden, Y. / 2001 / Untangling the ErbB signalling network / Nat. Rev. Mol. Cell Biol 2:127~137
Laskin, J. J. / 2004 / Epidermal growth factor receptor: a promising target in solid tumours / Cancer Treat. Rev 30:1~17
Herbst, R. S. / 2002 / Monoclonal antibodies to target epidermal growth factor receptor-positive tumors: a new paradigm for cancer therapy / Cancer 94:1593~1611
Capdevila, J. / 2009 / Anti-epidermal growth factor receptor monoclonal antibodies in cancer treatment / Cancer Treat. Rev 35:354~363
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