Current HER2-targeted therapies, including monoclonal antibody trastuzumab, are hindered by high cost of production, large molecular weight, and susceptibility to degradation.
A novel artificial antibody M-3-6-D has been developed by using a proper linker to dimerize two cyclic y-AApeptides, to mimic binding loops of monoclonal antibodies. M-3-6-D exhibited high affinity for HER2 and potently inhibited HER2 phosphorylation and downstream signal transduction. Treatment with M-3-6-D rivaled effects of trastuzumab in suppression of tumor growth in vivo. With the small molecular weight, resistance to proteolysis, as well as antibody-like properties, M-3-6-D could be a promising candidate for the development of novel antibody surrogates for the new generation of anti-cancer therapeutics.
Therapeutic efficacy of M-3-6 and M-3-6-D in SKBR3 xenograft models