Oncolytic viruses continue their march forwards...Harnessing CTLA4 as an approach to asthma

Todays Headlines from across the DailyUpdates network (10th July, 2006)

• Breaking News (from DailyUpdates-Technology): Oncolytic viruses continue their march forwards: Today’s featured press release is from Oncolytics Biotech who announce that it has commenced patient enrolment in its Phase Ib UK clinical trial investigating REOLYSIN in combination with radiation therapy as a treatment for patients with advanced cancers. REOLYSIN is human oncolytic reovirus currently in phase I/II development and has been demonstrated to replicate specifically in tumor cells bearing an activated Ras pathway (further information on this virus can be found in our report (Developments in oncolytic viruses - An emerging approach to cancer therapeutics). [Source:Oncolytics Biotech]

Featured Journal Article (from DailyUpdates-Immunology & Inflammatory Diseases): Harnessing CTLA4 as an approach to asthma: CTLA-4 is a negative regulator of T-cell costimulation that acts by preventing the interaction of CD80/86 on APCs with CD28 on T-cells. Interfering with this binding pair has been targeted successfully by Bristol-Myers Squibb’s who have developed abatacept and their second generation belatacept both of which are fusion proteins comprising the extracellular domain of the human CTLA4 molecule and the heavy-chain constant region of human IgG1. Abatacept initially demonstrated clinical efficacy in psoriasis however further development has been focused on rheumatoid arthritis with approval being granted by the FDA at the end of 2005. Belatacept (LEA29Y) appears to be a useful approach to both acute and chronic phases of graft rejection (for a detailed insight into CTLA4 based therapeutics see Autoimmune Disorders & Transplant Rejection - The Potential of T-cells Targeted Therapeutics). Today’s featured article focuses on research being conducted to utilize the cytoplasmic rather than the extracellular domain of CTLA-4 to suppress allergic inflammation. The Korean group, that have published their work in the May edition of Nature Medicine reported that engineering T cells to conditionally express this cytoplasmic domain markedly reduced infiltration of inflammatory cells, secretion of Th2 cytokines, serum IgE levels and airway hyper-responsiveness in a mouse model of allergic airway inflammation. Global asthma sales should continue grow, sharing a market worth $23 billion with COPD therapeutics by 2014. Inhaled corticosteroid/long-acting bronchodilator combinations are set to be the leading class by value in 2014, followed by leukotriene antagonists, and anticholinergics (see our feature on Asthma and COPD). Today’s featured research suggests that biologics focusing on the intracellular component of CTLA-4 may also feature in future pipelines for asthma candidates [Nat Med. 2006 May;12(5):574-9]