Novel Therapy for Hepatocellular Carcinoma

Panorama Research, Inc., Sunnyvale CA

Investigators

Abstract

[unreadable] DESCRIPTION (provided by applicant): [unreadable] Hepatocellular carcinoma (HCC) is among the world's most common and lethal malignancies with no effective therapy. Because of the normal function of the liver to detoxify xenobiotics, cancers of this tissue are notoriously resistant to chemotherapy. Furthermore, most patients do not tolerate therapies that might otherwise be effective due to underlying liver disease (i.e. cirrhosis, HBV, HCV infections etc.) To overcome these limitations, we propose to develop an antibody-based biopharmaceutical against a clinically validated HCC target. In contrast to conventional approaches, this therapy is a) tumor-specific (limited damage of normal tissue), and b) not susceptible to mechanisms of hepatocyte detoxification. The overall goal of this project is to develop a novel therapy for hepatocellular carcinoma (HCC). Compelling data from China support the development of HEPAMA-1, a 131I-labeled murine HCC-specific monoclonal antibody. Phase II studies (>100 patients) carried out by our collaborators from the Shanghai Institute of Biochemistry and Cell Biology indicate significant survival advantage among recipients of this therapy with minimal adverse effects, in contrast to conventional chemotherapeutic drugs. PRI exclusively licensed this technology with the intention to develop an improved version outside of China. The purpose of this grant is to support the preclinical development of an optimized form of this novel and important therapy. To this end, in Phase I we will humanize the antibody and identify the target antigen, then confirm high affinity HCC specific binding. Next we will produce a recombinant humanized antibody, optimize iodination, and carry out QC and stability studies. In phase II, we will study the anti-tumor activity of the 131-l-labeled antibody in xenograft models of HCC. The final goal of phase II will be to submit an IND and initiate phase l/ll human clinical studies of the improved, validated anti-HCC antibody. Based on the previous human studies, this [unreadable] antibody appears to be a promising novel therapy for HCC. [unreadable] [unreadable] [unreadable]