Dendreon Corp fka DNDNQ

[rancherho]

1. The median survival for both the Cumulative CD54 Cell Counts above median and for Cumulative CD54 Upregulation both appear to be approximately 30 months, but the Cell Count 36 month survival rate appears to be about 35% vs. the Upregulation survival rate of 45%.

2. The median stimulation index (T cell proliferation) when challenged by the PA2024 fusion antigen in the P11 trial measured 21 months post Provenge therapy and prior to a booster shot was 93.7 and when measured 13 weeks after the booster was 221.8. It's intriguing to consider the possible effect of such Provenge booster shots in further improving survival in AIPC.

3. For those of you into heavy duty science lectures and interested as to where all of these CD54 mature dendritic cells processed from peripheral blood monocytes go after infusion, the following lecture (with the assistance of pen, paper and the rewind key) is fascinating:
Migratory Properties and Immunological Consequences of Dendritic Cell Migration
Wednesday, October 25, 2006
Uli Von Andrian
Total Running Time: 01:03:39
http://videocast.nih.gov/PastEvents.asp?c=28

4. View this in the context that the NCI/Therion Phase 2 report on the PROSTVAC fowlpox based vaccine targeting PSA had a median stimulation index of 3.3, and that Dr. Rosenberg of the NCI was required to genetically engineer T cells used in adoptive cell therapy against melanoma to overexpress IL-2 and IL-15 in order for them to persist in vivo for more than 48 hours.

5. Dr. Von Adrian's data suggests that dendritic antigen presenting cells derived from blood monocytes accumulating in bone marrow, cannot enter the thymus, and are thus not subject to deletion/negative selection there, and are a source of long term memory T cells. The P11 data clearly suggests that monitoring a patient's T cell proliferation data as a function of time and boosting as it declines may be quite beneficial. Thus, the source of the progenitor cells as well as their CD54 expression characteristics might be of fundamental importance. For example, skin derived dendritic cells recruited at injection sites by the Therion, CEGE's GVAX and Onyxax's prostate cancer vaccines may be unable to stimulate such robust T cell proliferation and to maintain it over such long periods.

6. At the end of the Von Adrian lecture, he shows a real time video of fluorescently tagged cells (using B cells expressing a target antigen) to show how regulatory T cells prevent CD8 effector T cells from staying attached to target cells long enough to empty their destructive compounds into the target cell. This reduces their killing effect by a factor of 7. This impressive demonstration suggests the importance of controlling T regs, possibly with antibodies against CTLA4, PD1, LAG3, or ONTAK and Treg depletion strategies. The synergistic effect of Taxotere might also be related to its possible preferential destruction of Tregs.

7. IMHO, looking at the larger picture that this immunology data suggests, the ex vivo processing and maturation of blood monocytes creates a uniquely powerful T cell reaction, likely only modulated by Tregs. If so, with Treg control therapies advancing through various clinical trials, the potential for combining such adjuvants with DNDN vaccines appears extremely promising. JMHO.

Good luck to all DNDN longs.