Journal
MOLECULAR CANCER THERAPEUTICS
Volume 6, Issue 3, Pages 856-865Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1535-7163.MCT-06-0581
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- National Research Foundation of Korea [R21-2005-000-10023-0] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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 similar to 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.
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