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Bispecific small molecule–antibody conjugate targeting prostate cancer

2013; National Academy of Sciences; Volume: 110; Issue: 44 Linguagem: Inglês

10.1073/pnas.1316026110

1091-6490

Chan Hyuk Kim, Jun Y. Axup, Brian R. Lawson, Hwayoung Yun, Virginie Tardif, Sei Hyun Choi, Quan Zhou, Anna Dubrovska, Sandra L. Biroc, Robin Marsden, Jason Pinstaff, Vaughn V. Smider, Peter G. Schultz,

Cell Adhesion Molecules Research

Significance We have developed a semisynthetic method for the production of bispecific antibody-like therapeutics consisting of a small molecule targeting moiety conjugated to an antibody. A highly selective prostate-specific membrane antigen-binding ligand was site specifically conjugated to a mutant α cluster of differentiation 3 (αCD3) Fab containing an unnatural amino acid with orthogonal chemical reactivity. The optimized conjugate showed potent in vitro activity, good serum half-life, and potent in vivo activity in prostate cancer xenograft mouse models. This semisynthetic approach is likely to be applicable to the generation of additional bispecific agents using drug-like ligands selective for other cell-surface receptors.