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Trivalent and Trispecific Antibody Derivatives for Cancer Therapy

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Bispecific Antibodies

Abstract

This chapter highlights single-chain triplebodies (sctbs), recombinant proteins derived from single-chain Fv antibody fragments (scFvs), which carry three scFvs arranged in tandem in a single polypeptide chain. Sctbs carrying binding sites for two copies of the same antigen on the tumor cell are called “triplebodies with bivalent, mono-specific targeting.” Sctbs addressing two different target antigens on the same tumor cell plus a trigger molecule are “dual-targeting” agents. Prototype 19-16-19 is discussed as example of mono-targeting agent, specific for CD19 on B-lymphoid leukemia cells and recruiting natural killer (NK) cells and macrophages as cytotoxic effectors via the trigger CD16. The sctb 123-16-33 is a prototypical example of “dual-targeting” agent specific for CD123 and CD33 on acute myeloid leukemia cells. The anticipated benefits of dual- over mono-specific targeting and of the triplebody format in general are outlined.

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Correspondence to Ingo Schubert .

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Stein, C., Schubert, I., Fey, G.H. (2011). Trivalent and Trispecific Antibody Derivatives for Cancer Therapy. In: Kontermann, R. (eds) Bispecific Antibodies. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-20910-9_4

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