Preclinical evaluation of MORAb-003, a humanized monoclonal antibody antagonizing folate receptor-alpha

  • Cancer Immun. 2007 Mar 9;7:6.
Wolfgang Ebel  1 ,  Eric L Routhier ,  Brian Foley ,  Sara Jacob ,  Jennifer M McDonough ,  Rina K Patel ,  Howard A Turchin ,  Qimin Chao ,  J Bradford Kline ,  Lloyd J Old ,  Martin D Phillips ,  Nicholas C Nicolaides ,  Philip M Sass ,  Luigi Grasso
Affiliations
  • 1. Morphotek Inc., 210 Welsh Pool Road, Exton, PA, USA.
PMID: 17346028
Abstract

The highly restricted distribution of human folate receptor-alpha (FRalpha) 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 antibody-based immunotherapy for oncology indications. We have developed a therapeutic humanized monoclonal antibody with high affinity for FRalpha, 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 FRalpha. 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 non-human primates, MORAb-003 development has recently been advanced to clinical trials involving ovarian Cancer patients.

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