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Research Articles: Therapeutics, Targets, and Development

The glycotope-specific RAV12 monoclonal antibody induces oncosis in vitro and has antitumor activity against gastrointestinal adenocarcinoma tumor xenografts in vivo

Raven Biotechnologies, Inc., South San Francisco, California

Requests for reprints: Deryk Loo, Raven Biotechnologies, Inc., 1140 Veterans Boulevard, South San Francisco, CA 94080. Phone: 650-624-2636; Fax: 650-553-9169. E-mail: dloo{at}ravenbio.com

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 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. [Mol Cancer Ther 2007;6(3):856–65]

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Note: Current address for N. Pryer: Novartis Institute for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608.

¹ P. Young and J.P. Mather, in preparation.

Received 9/18/06; revised 12/11/06; accepted 1/25/07.

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