title: Chemically Programmed Bispecific Antibody Targeting Legumain Protease and αvβ3 Integrin Mediates Strong Antitumor Effects.
abstract: A chemically programmed bispecific antibody (cp-bsAb) that targeted cysteine protease legumain and αvβ3 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 legumain 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.
authors.affiliation: †Departments of Immunology and Microbial Sciences and §Cell and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: †Departments of Immunology and Microbial Sciences and §Cell and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Rajib K
authors.initials: RK
authors.lastname: Goswami
authors.affiliation: †Departments of Immunology and Microbial Sciences and §Cell and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Cheng
authors.initials: C
authors.lastname: Liu
authors.affiliation: †Departments of Immunology and Microbial Sciences and §Cell and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Subhash C
authors.initials: SC
authors.lastname: Sinha
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D057056:Cysteine Proteases / Q000378:metabolism*; D005260:Female; D005634:Fructose-Bisphosphate Aldolase / Q000378:metabolism*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism*; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D051379:Mice; D000099240:Asparaginyl Endopeptidase
chemical_list: D018033:Antibodies, Bispecific; D000970:Antineoplastic Agents; D003546:Cysteine Endopeptidases; D057056:Cysteine Proteases; D005634:Fructose-Bisphosphate Aldolase; D007140:Immunoglobulin Fab Fragments; D039302:Integrin alphaVbeta3; D000099240:Asparaginyl Endopeptidase; C109536:antibody aldolase
keywords: 38C2; aldolase; alpha(v)beta(3); antibody; bispecific; chemical; integrin; legumain; protease