Literature DB >> 17346028

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

Wolfgang Ebel1, 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.   

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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Year:  2007        PMID: 17346028      PMCID: PMC2935753     

Source DB:  PubMed          Journal:  Cancer Immun        ISSN: 1424-9634


  27 in total

1.  Influence of the route of administration on targeting of ovarian cancer with the chimeric monoclonal antibody MOv18: i.v. vs. i.p.

Authors:  I van Zanten-Przybysz; C F Molthoff; J C Roos; R H Verheijen; A van Hof; M R Buist; H M Prinssen; W den Hollander; P Kenemans
Journal:  Int J Cancer       Date:  2001-04-01       Impact factor: 7.396

2.  Cell surface antigens of human trophoblast and choriocarcinoma defined by monoclonal antibodies.

Authors:  W J Rettig; C Cordon-Cardo; J P Koulos; J L Lewis; H F Oettgen; L J Old
Journal:  Int J Cancer       Date:  1985-04-15       Impact factor: 7.396

Review 3.  Morphogenics as a tool for target discovery and drug development.

Authors:  Nicholas C Nicolaides; Wolfgang Ebel; Brad Kline; Qimin Chao; Eric Routhier; Philip M Sass; Luigi Grasso
Journal:  Ann N Y Acad Sci       Date:  2005-11       Impact factor: 5.691

4.  Cellular and humoral responses after multiple injections of unconjugated chimeric monoclonal antibody MOv18 in ovarian cancer patients: a pilot study.

Authors:  Iwona van Zanten-Przybysz; Carla Molthoff; Jacqueline Klein Gebbinck; Silvia von Mensdorff-Pouilly; Rob Verstraeten; Peter Kenemans; René Verheijen
Journal:  J Cancer Res Clin Oncol       Date:  2002-08-23       Impact factor: 4.553

5.  Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study.

Authors:  Robert F Ozols; Brian N Bundy; Benjamin E Greer; Jeffrey M Fowler; Daniel Clarke-Pearson; Robert A Burger; Robert S Mannel; Koen DeGeest; Ellen M Hartenbach; Rebecca Baergen
Journal:  J Clin Oncol       Date:  2003-07-14       Impact factor: 44.544

6.  Purification, properties, and immunological characterization of folate-binding proteins from human leukemia cells.

Authors:  E Sadasivan; M da Costa; S P Rothenberg; L Brink
Journal:  Biochim Biophys Acta       Date:  1987-07-16

7.  Reversion of transformed phenotype in ovarian cancer cells by intracellular expression of anti folate receptor antibodies.

Authors:  M Figini; R Ferri; D Mezzanzanica; M Bagnoli; E Luison; S Miotti; S Canevari
Journal:  Gene Ther       Date:  2003-06       Impact factor: 5.250

8.  Lyn is a target gene for prostate cancer: sequence-based inhibition induces regression of human tumor xenografts.

Authors:  Mirela Goldenberg-Furmanov; Ilan Stein; Eli Pikarsky; Hila Rubin; Shafika Kasem; Marc Wygoda; Irina Weinstein; Hadas Reuveni; Shmuel A Ben-Sasson
Journal:  Cancer Res       Date:  2004-02-01       Impact factor: 12.701

9.  Characterization of human ovarian carcinoma-associated antigens defined by novel monoclonal antibodies with tumor-restricted specificity.

Authors:  S Miotti; S Canevari; S Ménard; D Mezzanzanica; G Porro; S M Pupa; M Regazzoni; E Tagliabue; M I Colnaghi
Journal:  Int J Cancer       Date:  1987-03-15       Impact factor: 7.396

10.  Interaction of folate receptor with signaling molecules lyn and G(alpha)(i-3) in detergent-resistant complexes from the ovary carcinoma cell line IGROV1.

Authors:  S Miotti; M Bagnoli; A Tomassetti; M I Colnaghi; S Canevari
Journal:  J Cell Sci       Date:  2000-01       Impact factor: 5.285

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  58 in total

1.  Folate-immunoglobulin G as an anticancer therapeutic antibody.

Authors:  Hong Li; Yanhui Lu; Longzhu Piao; Jun Wu; Xiaojuan Yang; Sri Vidya Kondadasula; William E Carson; Robert J Lee
Journal:  Bioconjug Chem       Date:  2010-05-19       Impact factor: 4.774

Review 2.  Have we overestimated the benefit of human(ized) antibodies?

Authors:  Daniel R Getts; Meghann T Getts; Derrick P McCarthy; Emily M L Chastain; Stephen D Miller
Journal:  MAbs       Date:  2010-11-01       Impact factor: 5.857

3.  High expression of folate receptor alpha in lung cancer correlates with adenocarcinoma histology and EGFR [corrected] mutation.

Authors:  Maria Ines Nunez; Carmen Behrens; Denise M Woods; Heather Lin; Milind Suraokar; Humam Kadara; Wayne Hofstetter; Neda Kalhor; J Jack Lee; Wilbur Franklin; David J Stewart; Ignacio I Wistuba
Journal:  J Thorac Oncol       Date:  2012-05       Impact factor: 15.609

4.  The antitumor activity of the human FOLR1-specific monoclonal antibody, farletuzumab, in an ovarian cancer mouse model is mediated by antibody-dependent cellular cytotoxicity.

Authors:  JianMin Lin; Jared L Spidel; Christopher J Maddage; Katherine A Rybinski; Rina P Kennedy; Candice L M Krauthauser; Young Chul Park; Earl F Albone; Sara Jacob; Matthew T Goserud; Bryon P Martinez; Qimin Chao; Yuhong Zhou; Nicholas C Nicolaides; J Bradford Kline; Luigi Grasso
Journal:  Cancer Biol Ther       Date:  2013-08-28       Impact factor: 4.742

5.  Role of farletuzumab in epithelial ovarian carcinoma.

Authors:  Danijela Jelovac; Deborah K Armstrong
Journal:  Curr Pharm Des       Date:  2012       Impact factor: 3.116

6.  Antibodies to watch in 2010.

Authors:  Janice M Reichert
Journal:  MAbs       Date:  2010-01-16       Impact factor: 5.857

7.  Autoantibodies to folate receptor during pregnancy and neural tube defect risk.

Authors:  Robert M Cabrera; Gary M Shaw; Johnathan L Ballard; Suzan L Carmichael; Wei Yang; Edward J Lammer; Richard H Finnell
Journal:  J Reprod Immunol       Date:  2008-09-18       Impact factor: 4.054

Review 8.  Intraoperative imaging in ovarian cancer: fact or fiction?

Authors:  Lucia M A Crane; Marleen van Oosten; Rick G Pleijhuis; Arash Motekallemi; Sean C Dowdy; William A Cliby; Ate G J van der Zee; Gooitzen M van Dam
Journal:  Mol Imaging       Date:  2011-04-26       Impact factor: 4.488

Review 9.  Beyond chemotherapy: targeted therapies in ovarian cancer.

Authors:  Timothy A Yap; Craig P Carden; Stan B Kaye
Journal:  Nat Rev Cancer       Date:  2009-03       Impact factor: 60.716

10.  Significance of folate receptor alpha and thymidylate synthase protein expression in patients with non-small-cell lung cancer treated with pemetrexed.

Authors:  Daniel C Christoph; Bernadette Reyna Asuncion; Biftu Hassan; Cindy Tran; Julia D Maltzman; Daniel J O'Shannessy; Murry W Wynes; Thomas C Gauler; Jeremias Wohlschlaeger; Mathias Hoiczyk; Martin Schuler; Wilfried E Eberhardt; Fred R Hirsch
Journal:  J Thorac Oncol       Date:  2013-01       Impact factor: 15.609

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