Thanks for the informative post. Will ask more later about all that Th1/Th2 story; for now something more basic, when you say that:
CAT also ... selects their mAbs based on bioactivity and not just affinity.
While I certainly hope they do look at bioactivity, I wonder how they do it with, presumably, libraries of antibody fragments. It's no news that a MAb's ultimate activity is critically dependent on isotype and, to make it worse, this happens in ways that cannot always be easily predicted from the behavior of the fragments. So, unless they want to use the fragments themselves, I seriously doubt they can get full characterization of bioactivity unless they study the complete MAbs.
But if they study antibody activity with full MAbs, then that would imply that either:
(1) they have selected the genes of a few V domain pairs, from promising fragments, to make full MAbs first, or
(2) they can make large libraries of full MAbs, something I was not aware of.
If (1), then I see no big advantage in their approach versus using transgenic mouse-generated MAbs, which, of course, are always full molecules.
If (2), tell me again where to buy shares of this company -g-
Back to anti-TNF, Enbrel always struck me as kind of a contrived construct, but what about Remicade or the Celltech antibody? Have you looked at the RA data for those? One drawback of the former is the apparent need to use MTX, which one may not need to with humanized or human molecules. Here is the abstract of the Remicade (infliximab) phase III study:
ncbi.nlm.nih.gov
One last clarification re. Medarex. It has several, older, humanized Abs in trials; some if not all are bi-specific. I cannot recall off-hand. On the human (i.e. transgenic mice) front, I think they have an anti-CD4 already in phase I or very close to it (I am no fan of this; IDEC had lots of problems with their "primatized" molecules and Medarex has not presented anything, to my knowledge, to make me think that they are going to do any better). I do not know of the progress for anti-CTLA4 other than the PRs; you do not seem impressed with the potential of this one, care to elaborate? The larger issue that you make is a very good one; target selection is key, and CAT seems to have chosen two very good ones for their clinical projects, and this is independent of the merits of the technology per se.
Welcome to SI and here is hoping that we see more of your fine contributions.
PB |
