Medarex Announces Preclinical Data from Multiple Research Programs Demonstrating Anti-Tumor Activity in Cancer
- Data Presented at the American Association for Cancer Research -
PRINCETON, N.J., April 21 /PRNewswire-FirstCall/ -- Medarex, Inc. (Nasdaq: MEDX - News) today announced preclinical efficacy and safety data from multiple programs, including antibodies to novel and potentially important cancer targets (CXCR4, fucosyl-GM1, glypican-3, mesothelin, CD70) and additional research in the area of antibody-drug conjugates. Data from the studies were presented at the Annual Meeting of the American Association for Cancer Research (AACR), April 18-22, 2009, in Colorado.
Characterization of MDX-1338, a human anti-CXCR4 antibody proposed for therapeutic application in AML and ALL (Abstract #LB-150)
CXCR4 is a seven-transmembrane, G-protein-coupled receptor in the CXC chemokine receptor family that is expressed on a variety of cancers including leukemias, lymphomas, breast, lung, colon, pancreatic, and ovarian cancer. In preclinical studies, MDX-1338, a fully human anti-CXCR4 antibody, effectively blocked the binding of CXCR4 to its ligand, CXCL12, thereby inhibiting chemotaxis and migration responses. In addition, MDX-1338 also reduced tumor growth in acute myelogenous leukemia and lymphoma xenograft models.
Efficacy of MDX-1110, an anti-Fucosyl-GM1 antibody in a SCLC tumor model (Abstract #838)
Fucosyl-GM1 is a ganglioside, a component of the cell plasma membrane, that is expressed on most small cell lung cancers (SCLC). In in vitro preclinical studies, a fully human, non-fucosylated anti-fucosyl-GM1 antibody, MDX-1110, demonstrated robust cytotoxic effector function (both antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity) for killing tumor cells. Additionally, MDX-1110 showed a favorable safety and toxicity profile. MDX-1110 also demonstrated potent anti-tumor activity as a monotherapy and enhanced efficacy and improved control of tumor cell growth in combination with standard of care chemotherapy in in vivo studies.
Development of anti-Glypican 3 therapeutic antibodies (Abstract #1233)
Glypican-3 is a protein that has been shown to be expressed in liver cancer. A panel of fully human anti-glypican-3 antibodies was generated from which a lead candidate, MDX-1414, was selected for its high affinity, specificity, effector function and internalization properties. MDX-1414 demonstrated anti-tumor efficacy leading to significant and durable suppression of established subcutaneous tumors in a liver cancer xenograft model with no evidence of toxicity. Targeting glypican-3 with antibodies enhanced for antibody-dependent cell-mediated cytotoxicity properties, as drug-conjugates or used in combination with existing therapies, may represent a potentially important new treatment for liver cancer.
Efficacy and Toxicity of anti-mesothelin antibody drug conjugate (Abstract #3235)
Mesothelin is a glycoprotein over-expressed on mesotheliomas and other cancers, including ovarian and lung cancer, and because of its limited expression in normal tissue, it is an attractive target for an antibody-drug conjugate. In xenograft models of ovarian and lung cancer, MDX-1204, a fully human anti-mesothelin antibody-drug conjugate, demonstrated significant anti-tumor activity at doses as low as 0.3 umole/kg. In addition, the antibody-drug conjugate was well-tolerated in cynomolgous monkeys and mouse models.
The critical role of cleavable linkers for minor groove binding alkylating agent (MGBA) based antibody-drug conjugates (Abstract #1722)
The effectiveness of a cleavable linker over a non-cleavable linker when used with MGBA-based antibody-drug conjugates was examined using fully human anti-CD70 antibody-drug conjugates. In renal cancer xenograft models, single dose treatment with conjugates using the cleavable linker demonstrated selective and antigen-dependent killing of tumor cells leading to the regression of established tumors. Antibody-drug conjugates comprising a non-cleavable linker had greatly reduced specificity and efficacy. In addition to demonstrating potent anti-tumor efficacy, conjugates using a cleavable linker also showed a more favorable toxicity and safety profile over conjugates using a non-cleavable linker. |
