%0 Journal Article
%T Dual-Targeting for the Elimination of Cancer Cells with Increased Selectivity
%A Ingo Schubert
%A Christoph Stein
%A Georg H. Fey
%J Antibodies
%D 2012
%I MDPI AG
%R 10.3390/antib1010002
%X 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 ˇ°dual-targeting agentsˇ±. 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.
%K dual-targeting
%K cancer therapy
%K effector cell
%K triplebody
%K NK-cell
%K macrophage
%K drug conjugates
%U http://www.mdpi.com/2073-4468/1/1/2