title: Development of ASG-15ME, a Novel Antibody-Drug Conjugate Targeting SLITRK6, a New Urothelial Cancer Biomarker.
abstract: SLITRK6 is a member of the SLITRK family of neuronal transmembrane proteins that was discovered as a bladder tumor antigen using suppressive subtractive hybridization. Extensive immunohistochemistry showed SLITRK6 to be expressed in multiple epithelial tumors, including bladder, lung, and breast cancer as well as in glioblastoma. To explore the possibility of using SLITRK6 as a target for an antibody-drug conjugate (ADC), we generated a panel of fully human mAbs specific for SLITRK6. ADCs showed potent in vitro and in vivo cytotoxic activity after conjugation to Monomethyl Auristatin E or Monomethyl Auristatin F. The most potent ADC, ASG-15ME, was selected as the development candidate and given the product name AGS15E. ASG-15ME is currently in phase I clinical trials for the treatment of metastatic urothelial cancer. This is the first report that SLITRK6 is a novel antigen in bladder cancer and also the first report of the development of ASG-15ME for the treatment of metastatic bladder cancer. Mol Cancer Ther; 15(6); 1301-10. ©2016 AACR.
authors.affiliation: Agensys Inc., Santa Monica, California. kmorrison@agensys.com.
authors.forename: Kendall
authors.initials: K
authors.lastname: Morrison
authors.affiliation: Agensys Inc., Santa Monica, California.
authors.forename: Pia M
authors.initials: PM
authors.lastname: Challita-Eid
authors.affiliation: Agensys Inc., Santa Monica, California.
authors.forename: Arthur
authors.initials: A
authors.lastname: Raitano
authors.affiliation: Agensys Inc., Santa Monica, California.
authors.forename: Zili
authors.initials: Z
authors.lastname: An
authors.affiliation: Agensys Inc., Santa Monica, California.
authors.forename: Peng
authors.initials: P
authors.lastname: Yang
authors.affiliation: Agensys Inc., Santa Monica, California.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Abad
authors.affiliation: Agensys Inc., Santa Monica, California.
authors.forename: Wendy
authors.initials: W
authors.lastname: Liu
authors.affiliation: Agensys Inc., Santa Monica, California.
authors.forename: Dawn Ratay
authors.initials: DR
authors.lastname: Lortie
authors.affiliation: Agensys Inc., Santa Monica, California.
authors.forename: Josh T
authors.initials: JT
authors.lastname: Snyder
authors.affiliation: Agensys Inc., Santa Monica, California.
authors.forename: Linnette
authors.initials: L
authors.lastname: Capo
authors.affiliation: Agensys Inc., Santa Monica, California.
authors.forename: Alla
authors.initials: A
authors.lastname: Verlinsky
authors.affiliation: Agensys Inc., Santa Monica, California.
authors.forename: Hector
authors.initials: H
authors.lastname: Aviña
authors.affiliation: Agensys Inc., Santa Monica, California.
authors.forename: Fernando
authors.initials: F
authors.lastname: Doñate
authors.affiliation: Agensys Inc., Santa Monica, California.
authors.forename: Ingrid B J
authors.initials: IB
authors.lastname: Joseph
authors.affiliation: Agensys Inc., Santa Monica, California.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Pereira
authors.affiliation: Agensys Inc., Santa Monica, California.
authors.forename: Karen
authors.initials: K
authors.lastname: Morrison
authors.affiliation: Agensys Inc., Santa Monica, California.
authors.forename: David R
authors.initials: DR
authors.lastname: Stover
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D055808:Drug Discovery; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D051379:Mice; D009842:Oligopeptides / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D015854:Up-Regulation; D019459:Urothelium / Q000378:metabolism / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018796:Immunoconjugates; D008565:Membrane Proteins; D009842:Oligopeptides; C581991:Slitrk6 protein, human; C513576:monomethylauristatin F; C000620843:sirtratumab vedotin; C495575:monomethyl auristatin E