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

Antibodies

Ingo Schubert¹  Christoph Stein² 

[1] Department of Biology, University of Erlangen-Nuremberg, Erlangen 91058, Germany; E-Mails:;Department of Experimental Medicine and Immunotherapy, Institute of Applied Medical Engineering, Helmholtz Institute, RWTH, Aachen 52074, Germany

关键词: dual-targeting;    cancer therapy;    effector cell;    triplebody;    NK-cell;    macrophage;    drug conjugates;   

DOI  :  10.3390/antib1010002

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.