Article

Cancer Immunity, Vol. 7, p. 6 (9 March 2007) Submitted: 8 January 2007. Accepted: 19 February 2007.

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

Wolfgang Ebel1*, Eric L. Routhier1*, Brian Foley1, Sara Jacob1, Jennifer M. McDonough1, Rina K. Patel1, Howard A. Turchin1, Qimin Chao1, J. Bradford Kline1, Lloyd J. Old2, Martin D. Phillips1, Nicholas C. Nicolaides1, Philip M. Sass1 and Luigi Grasso1

1Morphotek Inc., 210 Welsh Pool Road, Exton, PA, USA

2Ludwig Institute for Cancer Research, 605 Third Avenue, New York, NY, USA

*These authors contributed equally to this work

Contributed by: LJ Old

Keywords: preclinical drug evaluation, monoclonal antibody, folate receptor, antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity

Abstract

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 antibody-based 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 non-human primates, MORAb-003 development has recently been advanced to clinical trials involving ovarian cancer patients.