Cancer Immunity (9 March 2007) Vol. 7, p. 6

The highly restricted distribution of human folate receptor-alpha (FRα) in normal tissues and its high expression in some tumors, along with its putative role in tumor cell transformation, make this antigen a suitable target for antigen-specific, monoclonal antibodybased immunotherapy for oncology indications. We have developed a therapeutic humanized monoclonal antibody with high affinity for FRα, named MORAb-003, which was derived from the optimization of the LK26 antibody using a whole cell genetic evolution platform. Here we show that MORAb-003 possesses novel, growth-inhibitory functions on cells overexpressing FRα. In addition, MORAb-003 elicited robust antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) in vitro, and inhibited growth of human ovarian tumor xenografts in nude mice. Because of its multimodal activity in vitro and its safe toxicology profile in nonhuman primates, MORAb-003 development has recently been advanced to clinical trials involving ovarian cancer patients.