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Drug platforms

Protease-resistant cytotoxic antibodies

Engineered, protease-resistant, cytotoxic, therapeutic antibodies could have better efficacy than nonresistant counterparts. In protease incubation assays, combined mutations in the CH2 and hinge region of an IgG1 increased stability compared with that of the parent antibody. In peripheral blood mononuclear cells, opsonized human lymphoma and adenocarcinoma cell lines, IgG1 antibodies that have mutations in the CH2 and hinge regions showed greater antibody-mediated cytotoxicity or antibody-dependent macrophage killing than IgG1 antibodies that have mutations in just one of the two regions. In nonhuman primates, the two-region mutant antibodies increased B cell depletion compared with saline. Next steps include testing the protease-resistant antibodies in preclinical models of cancer and autoimmune diseases.

SciBX 6(39); doi:10.1038/scibx.2013.1113
Published online Oct. 10, 2013

Patent and licensing status undisclosed

Kinder, M. et al. J. Biol. Chem.; published online Aug. 28, 2013;
doi:10.1074/jbc.M113.486142
Contact: Randall J. Brezski, Janssen R&D LLC, Spring House, Pa.
e-mail:

rbrezski@its.jnj.com