title: The glycotope-specific RAV12 monoclonal antibody induces oncosis in vitro and has antitumor activity against gastrointestinal adenocarcinoma tumor xenografts in vivo.
abstract: RAV12 is a chimeric antibody that recognizes an N-linked carbohydrate antigen (RAAG12) strongly expressed on multiple solid organ cancers. More than 90% of tumors of colorectal, gastric, and pancreatic origin express RAAG12, and a majority of these tumors exhibit uniform RAAG12 expression. RAV12 exhibits potent cytotoxic activity in vitro against COLO 205 colon tumor cells via an oncotic cell death mechanism. RAV12-treated COLO 205 cells undergo morphologic changes consistent with oncosis, including cytoskeletal rearrangement, rapid plasma membrane swelling, and cell lysis. RAV12 inhibited the growth of RAAG12-expressing gastrointestinal tumor xenografts in athymic mice. In the case of SNU-16 tumor cells, twice weekly treatment of established s.c. tumors with 10 mg/kg RAV12 caused a approximately 70% suppression of tumor growth at the end of the study. This preclinical data has led to the initiation of a phase I/IIA clinical study of RAV12 in patients with metastatic or recurrent adenocarcinoma.
authors.affiliation: Raven Biotechnologies Inc., 1140 Veterans Boulevard, South San Francisco, CA 94080, USA. dloo@ravenbio.com
authors.forename: Deryk
authors.initials: D
authors.lastname: Loo
authors.forename: Nancy
authors.initials: N
authors.lastname: Pryer
authors.forename: Peter
authors.initials: P
authors.lastname: Young
authors.forename: Tony
authors.initials: T
authors.lastname: Liang
authors.forename: Suzanne
authors.initials: S
authors.lastname: Coberly
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: King
authors.forename: Key
authors.initials: K
authors.lastname: Kang
authors.forename: Penny
authors.initials: P
authors.lastname: Roberts
authors.forename: Mary
authors.initials: M
authors.lastname: Tsao
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Xu
authors.forename: Beverly
authors.initials: B
authors.lastname: Potts
authors.forename: Jennie P
authors.initials: JP
authors.lastname: Mather
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005260:Female; D005333:Fetus; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006031:Glycosylation; D006801:Humans; D007114:Immunization; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction; D012097:Repressor Proteins / Q000276:immunology / Q000378:metabolism; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D016335:Zinc Fingers
chemical_list: D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate; D004268:DNA-Binding Proteins; D000939:Epitopes; D012097:Repressor Proteins; C485805:ZNF354C protein, human; C408086:Zfp354c protein, mouse