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Biotech, Institutes Discover Target for Multiple Tumors

EphA3 illustration (Protein Data Bank/Wikimedia Commons)

14 August 2014. Researchers in the U.S. and Australia identified an enzyme found in a range of cancerous tumor cells, but not normal adult tissue, and tested an engineered antibody to fight that enzyme in tumors. The team from the biotechnology company KaloBios Pharmaceuticals Inc. in South San Francisco, California, and Monash University and Ludwig Institute for Cancer Research, both in Melbourne, Australia published its findings in this week’s issue of the journal Cancer Research.

KaloBios develops engineered antibodies to treat cancer, cystic fibrosis, and asthma. One of its therapy candidates, code-named KB004, inhibits the actions of the gene Ephrin type-A receptor 3 or EphA3 that expresses an enzyme active in the development of many fetal organs, but also occurs in some blood-related cancers.

In the study led by Andrew Scott of the Ludwig Institute, the researchers found EphA3 enzymes over-expressed in the internal cellular environment of tumors. In tests where lab mice were grafted with human cancer cells, the team found EphA3 in stem cells derived from the mice’s bone-marrow, where the enzyme contributes to the growth of blood vessels feeding the tumors as well as the tumor’s supporting tissue.

Scott and colleagues also treated the cancer grafts with a specific antibody designed only to combat EphA3. The researchers found the antibody kills the stem cells in the tumors with EphA3. The antibody also severely disrupts the formation of blood vessels and supporting tissue in the tumors from cancer grafts. In addition, the researchers noted EphA3 appears only in the tumor cells and not in other cells in adult mice.

KB004 is now being tested in a combined early/intermediate-stage clinical trial with patients having several types of blood related cancers including various types of leukemia and multiple myeloma. In a company statement, Geoffrey Yarranton, KaloBios’s chief scientist and co-author of the paper, says the results of the study provide a rationale to expand the scope of KB004 to solid tumors as well as blood-related cancers.

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