Oxford Biomedica. 2005 to see 'Huge value creation' (Panmure Gordon)

A new paper for those who like to follow the science.

All that follows is IMHO, DYOR, no advice intended.

My comment is that these experiments suggest that IN A MOUSE MODEL antibodies are vitally important in the effectiveness of Trovax, as are CD4+ cells (helper T-cells). So it would suggest that the much vaunted CD8+ cells are not the only game in town. Doesn't mean they are not important too of course. And this is a mouse model system, not a human patient with a naturally occurring tumour. Having said that OXB would seem to have both angles covered, in that there is evidence of both humoral and cellular responses to Trovax in patients (thank you marwalker for your recent reply). Any comments marwalker, terry et al?


In a slightly different area, I suspect that the Wyeth/OXB product may well turn out to work. Would anyone like to comment on that from a scientific or financial point of view. I think it's been said that AK believes it was 'sold' a bit cheap?


rrr

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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]