Dendreon Corp fka DNDNQ

[rancherho]

One of the more interesting statements in the Statistics Section of the FDA Briefing materials for the Advisory Committee was that Provenge’s above median Total Nucleated Cell Count (TNC) had a statistically significant correlation with increased survival, whereas neither cumulative CD54 cell count nor cumulative CD54 upregulation did.CD54 (also known as ICAM-1) is the Provenge potency marker for the presence post ex vivo processing of mature dendritic cells (aka Antigen Presenting Cells or APCs) primed with the PA2024 fusion protein. DNDN made a poster presentation at a scientific conference last year showing apparent preliminary data that above median cumulative CD54 upregulation was prognostic for survival. Provenge is effectively a soup of a patient’s immune cells and in an average dose, only some 20% are APCs. The APCs are believed to prime CD8 effector T cells inducing a cellular th1 mediated immune response.The other immune cells in a Provenge dose include B cells, which in an immune context is related to an antibody, as opposed to a T cell,targeting mechanism and induces a th2 MofA. DNDN has also conducted early Ph1 trials of Neuvenge, which is processed ex vivo like Provenge, using a fusion protein incorporating the HER2/neu breast cancer antigen. A new study published in AACR reports that two experimental vaccines targeting either a antibody or T cell response: “individually conferred only weak tumor immunity. However, efficient tumor rejection was seen when neu and FLneu were combined, inducing both strong anti-HER2/neu-specific antibody and T cell responses. Adoptive transfer of both immune CD8+ T cells and immune sera from immunized mice was required to confer tumor immunity in naïve hosts. “ Antibody and CD8+ T Cell Responses against HER2/neu Required for Tumor Eradication after DNA Immunization with a Flt-3 Ligand Fusion Vaccine Clinical Cancer Research 13, 6195-6203, October 15, 2007. doi: 10.1158/1078-0432.CCR-07-0258 http://clincancerres.aacrjournals.org/cgi/content/abstract/13/20/6195
This may explain why a TNC count of processed immune cells, which includes activated B cells leading to an antibody response as well as APCs priming T cells, may be more relevant to extended survival than APCs alone as measured by their CD54 markers.
This might also suggest that at some point in the distant future DNDN’s Provenge, which has a stronger T cell response but a weaker antibody response against AIPC, may be combined with CEGE’s GVAX, which appears to have a stronger and broader antibody response, but weaker T cell response, to be twice as effective – with either docetaxel of ipilimumab countering the T cell defensive regulatory T cells. JMHO.