期刊
MOLECULAR PHARMACEUTICS
卷 12, 期 7, 页码 2544-2550出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.5b00257
关键词
aldolase; antibody; 38C2; alpha(v)beta(3); integrin; bispecific; chemical; legumain; protease
资金
- US Department of Defense [W81XWH-09-1-0690]
A chemically programmed bispecific antibody (cp-bsAb) that targeted Cysteine protease legumain and alpha v beta 3 integrin has been prepared using the aldolase antibody chemical programming (AACP) strategy. In vitro evaluation of the anti-legumain, anti-integrin cp-bsAb and its comparison with cpAbs targeting either integrin or leg-umain have shown that the former possesses superior functions, including receptor binding and inhibitory effects on cell proliferation as well as capillary tube formation, among all three cpAbs. The anti-legumain, anti-integrin cp-bsAb also inhibited growth of primary tumor more effectively than either anti-legumain or anti-integrin cpAb as observed in the MDA-MB-231 human breast cancer mouse model. The AACP-based cp-bsAb, which contains a generic aldolase antibody, can also serve as a suitable platform for combination therapy, where two equally potent compounds are used to target extracellular receptors.
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