A novel, native-format bispecific antibody triggering T-cell killing of B-cells is robustly active in mouse tumor models and cynomolgus monkeys.

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Smith EJ, Olson K, Haber LJ, Varghese B, Duramad P, Tustian AD, Oyejide A, Kirshner JR, Canova L, Menon J, Principio J, MacDonald D, Kantrowitz J, Papadopoulos N, Stahl N, Yancopoulos GD, Thurston G, Davis S

A novel, native-format bispecific antibody triggering T-cell killing of B-cells is robustly active in mouse tumor models and cynomolgus monkeys.

Sci Rep. 2015 Dec 11;5:17943. doi: 10.1038/srep17943.

PubMed ID

26659273 [ View in PubMed

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Abstract

Bispecific antibodies, while showing great therapeutic potential, pose formidable challenges with respect to their assembly, stability, immunogenicity, and pharmacodynamics. Here we describe a novel class of bispecific antibodies with native human immunoglobulin format. The design exploits differences in the affinities of the immunoglobulin isotypes for Protein A, allowing efficient large-scale purification. Using this format, we generated a bispecific antibody, REGN1979, targeting the B cell marker, CD20, and the CD3 component of the T cell receptor, which triggers redirected killing of B cells. In mice, this antibody prevented growth of B cell tumors and also caused regression of large established tumors. In cynomolgus monkeys, low doses of REGN1979 caused prolonged depletion of B cells in peripheral blood with a serum half-life of approximately 14 days. Further, the antibody induced a deeper depletion of B cells in lymphoid organs than rituximab. This format has broad applicability for development of clinical bispecific antibodies.

DrugBank Data that Cites this Article

Drugs

Odronextamab

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Odronextamab	B-lymphocyte antigen CD20	Protein	Humans	Yes	Binder	Details
Odronextamab	T-cell surface glycoprotein CD3 (Protein Group)	Protein group	Humans	Yes	Binder	Details