The publication reveals a novel mechanism which isolated tumour cells use to invade healthy brain tissue during the development and growth of glioblastoma multiforme (GBM), the most common and aggressive type of primary brain tumours. This mechanism involves the CD95/CD95L death system, which - when triggered - normally induces controlled cell death (apoptosis). Dr Martin-Villalba and her colleagues were able to demonstrate that, contrary to widely held beliefs, glioblastoma tumour cells take advantage of the CD95/CD95L system to increase their capacity to infiltrate healthy tissue. As a result, inhibition rather than induction of this system should be considered as a therapy for GBM.

“We found that glioblastoma cells induce the expression of so-called CD95 ligands in surrounding healthy tissue,” said Martin-Villalba, lead author of the study and Apogenix’s scientific advisor. “This ligand activates CD95, a death receptor on the surface of the tumour cells. However, instead of inducing apoptosis, triggering CD95 on glioblastoma cells leads to the induction of enzymes that, among other effects, facilitate the invasion of tumour cells in surrounding tissue. We have already shown in animal models that the neutralization of CD95 activity dramatically reduces the number of infiltrating GBM cells.”

New perspectives

“Over the last three years, the development of treatment strategies in GBM has not led to a notably improved survival rate,” added Dr. Thomas Höger, CEO of Apogenix. “Dr Martin-Villalba’s findings open up new perspectives for treatment options for GBM patients using our lead drug candidate APG101.”

APG101, a soluble fusion protein in humans that combines the extracellular domain of the CD95 receptor and the Fc portion of IgG, blocks the CD95/CD95L system by binding to the ligand. At present, Apogenix is developing the compound for the prevention of acute graft-versus-host disease (aGvHD). Apogenix was granted orphan drug status by the European Commission in 2006 for this indication and has plans to initiate clinical phase I studies in the first half of 2008.

“It is assumed that the infiltration of tumour cells into the surrounding brain areas is responsible for GBM tending to be refractory to treatment. We have already shown in animal models that APG101 successfully blocks the invasive behaviour of GBM cells. Apogenix is now looking to advance APG101 to clinical trials and to explore the drug’s potential benefit to patients,” said Dr. Harald Fricke, CMO of Apogenix.

The study published in Cancer Cell was conducted by Dr. Martin-Villalba of the German Cancer Research Centre (DKFZ) and colleagues from the DKFZ, the Universities of Heidelberg and Mannheim and Apogenix.

Source: Apogenix press release - 10. 03. 2008 (EJ) (P)

Further information:
Dr. Thomas Höger
Apogenix GmbH
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D-69120 Heidelberg
Tel.: +49 (0)6221-586 08 0
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E-mail: contact@apogenix.com