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用于乳腺癌和卵巢癌治疗的抗粘蛋白抗体人源化

Humanization of an anti-mucin antibody for breast and ovarian cancer therapy.

作者信息

Baker T S, Bose C C, Caskey-Finney H M, King D J, Lawson A D, Lyons A, Mountain A, Owens R J, Rolfe M R, Sehdev M

机构信息

Celltech Research Division, Celltech Ltd., Slough, Berks, U.K.

出版信息

Adv Exp Med Biol. 1994;353:61-82. doi: 10.1007/978-1-4615-2443-4_8.

Abstract

Antibody-drug conjugates utilize the targetting potential of antibodies to improve the potential of cytostatic or cytocidal drugs. One such murine monoclonal antibody, CTM01 (mCTM01), which recognizes an epitope on breast epithelial mucin, has potential for the treatment of breast and ovarian cancers. We examine in this paper the comparative properties of mCTM01 against a number of other anti-mucin antibodies. We then describe the humanization and high level re-expression of humanized CTM01 (hCTM01), a process designed to avoid the immune response to administered murine antibodies in human patients and to produce sufficient material for clinical studies. We show that the humanized form has properties superior to mCTM01 in terms of binding affinity to antigen presented on tumour cells.

摘要

抗体药物偶联物利用抗体的靶向潜力来提高细胞生长抑制剂或细胞杀伤药物的潜力。一种这样的鼠单克隆抗体CTM01(mCTM01),它识别乳腺上皮粘蛋白上的一个表位,具有治疗乳腺癌和卵巢癌的潜力。在本文中,我们研究了mCTM01与其他一些抗粘蛋白抗体相比的特性。然后我们描述了人源化CTM01(hCTM01)的人源化和高水平重新表达,该过程旨在避免人类患者对所施用的鼠抗体产生免疫反应,并产生足够的材料用于临床研究。我们表明,就与肿瘤细胞上呈现的抗原的结合亲和力而言,人源化形式具有优于mCTM01的特性。

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