Purified Ephrin Receptor Blocks Lymphoma Growth in Mouse Model

Cancer researchers have blocked the development of follicular lymphoma (FL) by injecting mice xenografted with human lymphomas with a purified tumor suppressing protein that is absent in 72% of FLs.

The ephrin (Eph) receptor A7 (EPHA7) is a tumor suppressor in follicular lymphoma and has been found to be inactivated in 72% of FLs. Eph receptors are components of cell signaling pathways involved in animal growth and development, forming the largest sub-family of receptor tyrosine kinases (RTKs). The extracellular domain of an Eph receptor interacts with ephrin ligands, which may be tethered to neighboring cells. Ligand-mediated activation of Ephs induces various important downstream effects and Eph receptors have been studied for their potential roles in the development of cancer.

In the current study, investigators at of Memorial Sloan-Kettering Cancer Center (New York, NY, USA) isolated and purified EPHA7 for use as a potential chemotherapeutic agent to treat FL.

They reported in the October 28, 2011, issue of the journal Cell that administration of the purified EPHA7TR protein produced antitumor effects against xenografted human lymphomas. The potency of the drug could be increased by fusing it to the anti-CD20 antibody (rituximab), which directly targeted the tumor suppressor to lymphomas in vivo.

“We went all the way from genomic data to a potential new drug,” said senior author Dr. Hans-Guido Wendel, professor of cancer biology and genetics at Memorial Sloan-Kettering Cancer Center. “EPHA7 was not on anyone's radar screen for lymphoma. Now it is. It is important that EPHA7 is a soluble factor. You can purify it, put it in a bottle, and see if it can be administered as a drug.”

“With access to tumor genomic data, suddenly we can do this; we know what has changed, and the question now is to define which changes are really important,” said Dr. Wendel. “With that information, we can start to develop new therapies.”

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Memorial Sloan-Kettering Cancer Center