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Antibodies 2012, 1(1), 2-18; doi:10.3390/antib1010002
Review

Dual-Targeting for the Elimination of Cancer Cells with Increased Selectivity

1,†
, 2,†,*  and 1
Received: 28 February 2012; in revised form: 16 March 2012 / Accepted: 30 March 2012 / Published: 10 April 2012
(This article belongs to the Special Issue Bispecific Antibodies for Dual Targeting Strategies)
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Abstract: Here we review recombinant proteins with a capability for dual-targeting. These molecules address two different antigens on the same tumor cell and therefore are called “dual-targeting agents”. By virtue of binding a chosen pair of antigens on the malignant cell, preferential binding to antigen double-positive over single-positive cells can be achieved when both are present in the same environment. Therapeutic effects of such agents are based on different modes of action: (1) They can act as pro-apoptotic agents or by inhibiting pro-survival signals; (2) The dual recognition moiety can be fused to effector-domains, such as bacterial toxins or other drugs, leading to the generation of bispecific antibody-drug conjugates (ADCs); (3) Dual-targeting agents can further be used to redirect an effector-cell to the tumor. A new generation of scFv-derived fusion proteins are the tandem single chain triplebodies (sctbs), which carry two scFv binding sites for antigens on the tumor cell plus a third, specific for a trigger molecule on an effector cell. The ability of preferential or selective targeting of antigen double-positive over single-positive cells opens attractive new perspectives for the use of dual-targeting agents in cancer therapy, and possibly also for the treatment of certain inflammatory and autoimmune disorders.
Keywords: dual-targeting; cancer therapy; effector cell; triplebody; NK-cell; macrophage; drug conjugates dual-targeting; cancer therapy; effector cell; triplebody; NK-cell; macrophage; drug conjugates
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Schubert, I.; Stein, C.; Fey, G.H. Dual-Targeting for the Elimination of Cancer Cells with Increased Selectivity. Antibodies 2012, 1, 2-18.

AMA Style

Schubert I, Stein C, Fey GH. Dual-Targeting for the Elimination of Cancer Cells with Increased Selectivity. Antibodies. 2012; 1(1):2-18.

Chicago/Turabian Style

Schubert, Ingo; Stein, Christoph; Fey, Georg H. 2012. "Dual-Targeting for the Elimination of Cancer Cells with Increased Selectivity." Antibodies 1, no. 1: 2-18.

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