PB:
Thanks, you saved me a ton of work.
No, I have absolutely nothing against the molecule. It was mouse when a collaborator worked with it, but..... affinity retained as an assumption, it should be fine. BTW....... Dr. Mike Collins at Bayer, a super microbiologist, showed that Listeria infections were enhanced in animals that rec'd this (murine version) MAb. No big deal you say? This was **1987**.
I'm not saying that CNTO or IMNX have been trying to hide anything, but it's been inside knowledge all along that TNF is protective early in infections and that, under given circumstances, anti-TNF was potentially really, really, really, really bad. Of course, CNTO also brought us that pile, HA-1A.
But, I am in the camp which believes that anti-TNF does more good than harm.
Back to Mike Collins..... I was very lucky. I went to Cutter and found this guy who had set up *the* most sensitive assays for protection against Gram-negatives. The guy was amazing, and had models absolutely standardized so that they were reproducible, one experiment to the next.... not an easy trick with anti-infectives. My labs made a sensational MAb that was potently neutralizing for a given wound isolate of Proteus mirabilis. In non-immunosuppressed animals, you could almost not cause a lethal infection.... you virtually had to give enough bugs such that it was equivalent to endotoxin poisoning. However, he had established a model where 2-3 cells were fatal, and where this really wonderful anti-flagellar MAb was highly protective. Of course, serotype-specific anti-LPS MAbs were also highly protective.
I credit Dr. Collins with my clear vision of anti-Gram-negative serology ever since. You can imagine my horror when I moved to XOMA and inherited E5, which was already in the clinic. You can perhaps also understand my lack of respect for PFE.
Those were great days. We were working in collaboration with Mark Lostrom (now CEO of a start-up) and Tony Siadak at Genetic Systems (subsequently Oncogen, subsequently Bristol-Myers Squibb Research Institute). They had Mae (?) Rostok and a few others in the lab who just busted their butts for two years. We were wading in anti-LPS MAbs, murine and truly human, that were protective at nanogram doses. Gazillions of them. Moreover, these guys/gals weren't pansies..... these human MAbs were derived from EBV transformants.
We were so far out in front of everyone else it was silly. Bayer blew all of that away by insisting on control from Germany, control by individuals that couldn't even spell s-e-r-o-l-o-g-y.
- g -
Anti-CD33? Lineage-specific, misses lymphs. Why not?
Cheers! (and thanks again) Rick |
