Walldiver:
1. I certainly don't want to take anyone's nose away from their chosen grindstones to consider the future, but there are several points covered by the ASCO videos that touch on issues that are relevant now.
2. Therion's conducted a blinded, randomized Ph2 trial of about the same size (125 vs. 127 enrollees)as the 9901 Provenge trial, with the same 2:1 ITT to control ratio. Their trial used a vaccine targeting PSA with a TRICOM adjuvant (CD54/ICAM-1, LFA and B7) that was in development in conjunction with the NCI for over a decade. Dr. Kantoff can criticize 9901 as being a small trial, but in spite of all Therion's perceived advantages, it failed to achieve statistical significance for either TTP or survival.
3. While the use of allogenic vaccines such as CEGE's GVAX may ultimately provide clinical benefits, they represent, to some extent, a roll of the antigen dice since there is little, if any, control over the antigens taken up by the dendritic cells recruited at their injection sites. The use of MDX-010 with them and the greatly increased immune DTH reactions at the injection sites emphasize that point.
4. The comments of Dr. Charles Drake of John Hopkins, IMO, are particularly noteworthy. They are the first that I've heard or read discussing the issue that the level of regulatory T cells in prostate tissue in AIPC, capable of rendering attacking CD8 T cells anergic, is 3 times the level in normal tissue. That would go a long way towards answering the NCI's oft repeated critique of all therapeutic cancer vaccines as applied to Provenge in AIPC: "If there are no objective tumor responses or complete remissions early on following therapy that would indicate cytotoxicity, how can a vaccine that doesn't kill cancer cells extend survival?". IMO, the primary reason lies in the ability of memory T cells primed by CD54 expressing dAPC's to home to secondary lymphoid tissues, blocking metastases to visceral organs and killing cancer cells unprotected by elevated levels of regulatory T cells. When asked by the CBER Advisory Committee in February why CD54 was chosen as a potency marker for Provenge and why it should be correlated with long term survival, DNDN's Dr. Provost replied in a self deprecating manner that perhaps DNDN was just lucky. The next time that question is asked, there should be more thought, supporting data and analysis offered in response. JMHO.
Good luck to all DNDN longs.
