iwfal:
>>To my knowledge **ALL** active immunotherapies show a strong correlation between some measure of immune responsiveness to vaccine and survival.<<
Don't have time to provide referemces, but in fact there has been a frustratingly large disconnect between immune responses and statistical increases in survival. In fact, one of the mysteries with Provenge is that it is difficult to measure a T cell stimulation response against human PAP, its putative target antigen. As a result, T cell response to the PA2024 fusion protein, which is not found in nature is used. The excitement about Provenge CD54 cell count, CD54 upregulation and Total Nucleated Cell count relationship to survival is due in part because there is such a poor relationship between human PAP expression and results.
All of this is not surprising, however, since antibody responses or T cell stimulation when testing serum deals with the "offense" of an adaptice immune attack rather than the "defense" of regulatory T cells as well as other immunosuppressive factors in the microenvironment surrounding a tumor. As my last Ihub post concerning the NIH video webcast of STAT3 expression detailed, STAT 3 expression has the ability not only to stimulate angiogenesis in the tumor microenvironment, but also to turn immune cells attacking cancer into defenders. The significant independent post randomization variable, that both DNDN's analysis and CEGE's analysis fail to account for, is the subsequent use of Taxotere that not only depletes rapidly proloferating regulatory T cells in the tumor microenvironment, but also activates macrophages, which are the primary weapon of choice that the B cell arm of the adaptive immune system uses to destroy antibody marked cancer cells. Without such breaking of tolerance, IMO, neither Provenge nor GVAX alone would be statistically significant for increased survival.
With due respect to your healthy and well deserved skepticism about biotech hype and obvious statistical expertise, I stand by my opinion that the identification of two antigens derived from metastatic AIPC cell lines that GVAX produces a strong antibody response to increased survival, with the adjuvant effects of Taxotere in long surviving Phase 2 GVAX patients, makes a strong case for scientific validation of the technology. Unfortunately, any statistically significant validation of that opinion must await the final Vital 1 results now projected to occur in 2H09.
