PB:
I think that you know this, but I did work with methylcholantrene-induced sarcomas. Very clean system, tumors frozen after only one pass. Fisher rats. No work done with cancer beyond third pass, three good cancers of independent origin, allowing for cross-immunization in each experiment and unambiguous results (got the same take home lessons as a few "mouse groups" that had definitive results well before me, but using rats..... not trying to take credit for anything novel). That is, I know that cancers can be strongly immunogenic, and that one can see strong concomitant resistance at a second site in an animal with a tumor that has overcome immune surveillance. So I certainly can't say that Schreiber is wrong. In fact, I wouldn't disagree with anything that is written in that profile. It's just that I don't think that it matters much with most spontaneous cancers, as I don't believe that there is an obligate need for most cancers to escape immune surveillance..... no strong antigens there to begin with. And I don't believe that anti-CTLA-4 is leading some last minute charge against one of every ten Vogelstein-like differences, that the patient is making an effective response against thousands of antigens to which he was previously masked.
I am guessing that the patient shown in those slides is an exception, that the progenitor cell that led to those tumors was strongly immunogenic and yet the tumors did escape surveillance.
Since Schreiber is proposing to use MAbs (Igenica), and since he's talking SPECIFIC anti-cancer responses, you'd think that he's targeting GIVEN ANTIGENS, and that they are not self antigens with limited distribution. Good luck with that brand new concept.
(You and I both know that I have 20 year old oars in the water, and that I've gotten away with harsh predictions for far too long. Would absolutely love a "modern-day versed" cancer immunologist to come along and give that "unequivocal" evidence for the dogma that has floated -- for sooooo long -- so many b.s. biotech efforts. Sincerely!)
Best! Rick |
