title: Successful eradication of established peritoneal ovarian tumors in SCID-Beige mice following adoptive transfer of T cells genetically targeted to the MUC16 antigen.
abstract: OBJECTIVE
  Most patients diagnosed with ovarian cancer will ultimately die from their disease. For this reason, novel approaches to the treatment of this malignancy are needed. Adoptive transfer of a patient's own T cells, genetically modified ex vivo through the introduction of a gene encoding a chimeric antigen receptor (CAR) targeted to a tumor-associated antigen, is a novel approach to the treatment of ovarian cancer.
  
  
  METHODS
  We have generated several CARs targeted to the retained extracellular domain of MUC16, termed MUC-CD, an antigen expressed on most ovarian carcinomas. We investigate the in vitro biology of human T cells retrovirally transduced to express these CARs by coculture assays on artificial antigen-presenting cells as well as by cytotoxicity and cytokine release assays using the human MUC-CD(+) ovarian tumor cell lines and primary patient tumor cells. Further, we assess the in vivo antitumor efficacy of MUC-CD-targeted T cells in SCID-Beige mice bearing peritoneal human MUC-CD(+) tumor cell lines.
  
  
  RESULTS
  CAR-modified, MUC-CD-targeted T cells exhibited efficient MUC-CD-specific cytolytic activity against both human ovarian cell and primary ovarian carcinoma cells in vitro. Furthermore, expanded MUC-CD-targeted T cells infused through either i.p. injection or i.v. infusion into SCID-Beige mice bearing orthotopic human MUC-CD(+) ovarian carcinoma tumors either delayed progression or fully eradicated disease.
  
  
  CONCLUSIONS
  These promising preclinical studies justify further investigation of MUC-CD-targeted T cells as a potential therapeutic approach for patients with high-risk MUC16(+) ovarian carcinomas.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Alena A
authors.initials: AA
authors.lastname: Chekmasova
authors.forename: Thapi D
authors.initials: TD
authors.lastname: Rao
authors.forename: Yan
authors.initials: Y
authors.lastname: Nikhamin
authors.forename: Kay J
authors.initials: KJ
authors.lastname: Park
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Levine
authors.forename: David R
authors.initials: DR
authors.lastname: Spriggs
authors.forename: Renier J
authors.initials: RJ
authors.lastname: Brentjens
mesh_terms: D000818:Animals; D018394:CA-125 Antigen / Q000235:genetics / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D018394:CA-125 Antigen; C451759:MUC16 protein, human; D008565:Membrane Proteins