APOTHERAPY - CD40 ligand-based modalities for the treatment of solid tumours. (Life sciences, genomics and biotechnology for health) (2006-10-01 - 2009-09-30)(»add to infobox)
ACRONYM:
APOTHERAPY
BUDGET:
2.108.500 €
FUNDING:
1.895.900 €
INSTRUMENT:
Specific Targeted Research Project
PROGRAMME:
Life sciences, genomics and biotechnology for health
The objective of this Apotherapy Specific Targeted Research Project proposal is to establish a European collective of international scientific excellence to combat cancer by translating basic research on key apoptotic pathways into tools which will improve the treatment and quality of life of cancer sufferers. The project will specifically aim to exploit the widespread expression of CD40, a TNF receptor family member, in human tumours and develop CD40 ligand-based modalities with high therapeutic potential and minimal side-effects. These translational studies are based on accumulating in vitro evidence suggesting that the activation of CD40 results in reduced proliferation and apoptosis induction selectively in cancer cells. The proposed STREP will develop vehicles for the efficient delivery of CD40L, such as CD40L-encapsulated liposome formulations and recombinant adenoviruses expressing CD40L and examine their in vitro and in vivo effects on tumour cell growth and metastasis. Apoptosis induced by CD40 engagement is dramatically augmented in the presence of inhibitors of the phosphoinositide 3-kinase (PI3 kinase) pathway which is frequently found activated in human tumours. The proposed STREP will expand on the development of inositol polyphosphates, novel PI3 kinase antagonists, and evaluate their in vitro and in vivo capacity to kill tumour cells and to amplify the CD40L-mediated effects on carcinoma cell growth, angiogenesis and metastasis. These studies will provide essential information for progressing the potential therapeutic strategy towards future clinical trials for the benefit of cancer sufferers.
