Oxford Biomedica. 2005 to see 'Huge value creation' (EVO) (OXB)

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Cancer Immunol Immunother. 2005 Nov 26;:1-10 [Epub ahead of print]

Active treatment of murine tumors with a highly attenuated vaccinia virus expressing the tumor associated antigen 5T4 (TroVax) is CD4(+) T cell dependent and antibody mediated.

Harrop R, Ryan MG, Myers KA, Redchenko I, Kingsman SM, Carroll MW.

Oxford BioMedica (UK) Ltd, The Medawar Centre, Oxford Science Park, OX4 4GA, Oxford, UK, r.harrop@oxfordbiomedica.co.uk.

5T4 is a tumor associated antigen that is expressed on the surface of a wide spectrum of human adenocarcinomas. The highly attenuated virus, modified vaccinia Ankara, has been engineered to express human 5T4 (h5T4). In a pre-clinical murine model, the recombinant virus (TroVax) induces protection against challenge with CT26-h5T4 (a syngeneic tumor line expressing h5T4). Anti-tumor activity is long lived, with protection still evident 6 months after the final vaccination. In a therapeutic setting, injection of mice with TroVax results in a reduction in tumor burden of >90%. Depletion of CD8(+) T cells has no effect upon therapy in the active treatment model, whereas depletion of CD4(+) T cells completely abrogates anti-tumor activity. In a prophylactic setting, depletion of CD4(+) and CD8(+) T cells after the induction of a h5T4 immune response has no deleterious effect on protection following challenge with CT26-h5T4. In light of these studies, the role of antibodies in protection against tumor challenge was investigated. 5T4 specific polyclonal serum decreased tumor burden by approximately 70%. Thus, we conclude that CD4(+) T cells are essential for the induction of a protective immune response and that antibodies are the likely effector moiety in this xenogeneic murine tumor model.

PMID: 16311730 [PubMed - as supplied by publisher]

Clin Sci (Lond). 2006 Jan 1;110(1):37-46.

Gene therapy for neurodegenerative and ocular diseases using lentiviral vectors.

Ralph GS, Binley K, Wong LF, Azzouz M, Mazarakis ND.

Oxford Biomedica plc, The Medawar Centre, Oxford Science Park, Oxford OX4 4GA, U.K.

Gene therapy holds great promise for the treatment of a wide range of inherited and acquired disorders. The development of viral vector systems to mediate safe and long-lasting expression of therapeutic transgenes in specific target cell populations is continually advancing. Gene therapy for the nervous system is particularly challenging due to the post-mitotic nature of neuronal cells and the restricted accessibility of the brain itself. Viral vectors based on lentiviruses provide particularly attractive vehicles for delivery of therapeutic genes to treat neurological and ocular diseases, since they efficiently transduce non-dividing cells and mediate sustained transgene expression. Furthermore, novel routes of vector delivery to the nervous system have recently been elucidated and these have increased further the scope of lentiviruses for gene therapy application. Several studies have demonstrated convincing therapeutic efficacy of lentiviral-based gene therapies in animal models of severe neurological disorders and the push for progressing such vectors to the clinic is ongoing. This review describes the key features of lentiviral vectors that make them such useful tools for gene therapy to the nervous system and outlines the major breakthroughs in the potential use of such vectors for treating neurodegenerative and ocular diseases.

PMID: 16336203 [PubMed - as supplied by publisher]