The glycotope-specific RAV12 monoclonal antibody induces oncosis in vitro and has antitumor activity against gastrointestinal adenocarcinoma tumor xenografts in vivo.
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.
Loo
Deryk
D
Raven Biotechnologies Inc., 1140 Veterans Boulevard, South San Francisco, CA 94080, USA. dloo@ravenbio.com
Pryer
Nancy
N
Young
Peter
P
Liang
Tony
T
Coberly
Suzanne
S
King
Kathleen L
KL
Kang
Key
K
Roberts
Penny
P
Tsao
Mary
M
Xu
Xiaolin
X
Potts
Beverly
B
Mather
Jennie P
JP
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
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