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The TI Pharma program 'TNF ligands in cancer' delivered and validated a set of monoclonal antibodies targeting TNF family members. In this Value Creation Project the therapeutic potential of these antibodies for the treatment of cancer is evaluated.
Cancer is still one of the leading causes of death. The high incidence of cancer in Europe, resistance of many cancer types to current treatments combined with the struggle to find effective new medicines by the pharmaceutical industry asks for increased research efforts to deliver novel therapies. Targeting members of the TNF (receptor) superfamily may provide such novel therapies. TNF (receptor) superfamily members are expressed on cells of the immune system and are known to modulate their activity, for example in response to antigens. Co-stimulation via TNF (receptor) superfamily members triggers a diverse array of cellular responses most of which relate to the decision between cell survival and cell death. The feasibility of developing biopharmaceuticals that modulate TNF (receptor) superfamily members has been established by the therapeutic and commercial success of targeting TNF-alpha for the treatment of Rheumatoid Arthritis and related diseases. Receptors of the TNF (receptor) superfamily are commonly expressed in a wide variety of cancers. Therefore, TNF receptor family members or their cognate ligands are pursued as targets in the field of Oncology to either 1) directly induce cell-death through activation of so-called Death Receptors or by delivering a toxic payload to tumor cells, or 2) indirectly by withdrawal of tumor pro-survival factors or enhancement of anti-tumor immunity.
Antibodies have been developed that target members of the TNF signaling network thereby enhancing pro-apoptotic signaling of TRAIL, anti-tumor immunity or minimizing pro-survival signaling of other TNF ligands. Further research is necessary to elucidate the mechanism of action and the therapeutic potential of these antibodies. In addition, the identification of biomarkers that can be used for patient group selection will be valuable for the successful development of new cancer therapies.
Full project title: Developing antibodies targeting TNF family members into clinical candidates for treatment of cancer
Start date: 1 January 2012
End date: 31 December 2013
Goal: Develop a monoclonal antibody therapy for treatment of cancer
Principal investigator: Hans van Eenennaam
Project size: 8 FTE's
Project budget: 1.707 k€
Partners: BioNovion, AMC, NKI, UMCG
Valeria Lascano (project T3-504)
The role of APRIL (TNFSF13) in carcinogenesis