Indications -- Psoriasis/Chronic Inflammation Message Board

STOCKTALK

We've detected that you're using an ad content blocking browser plug-in or feature. Ads provide a critical source of revenue to the continued operation of Silicon Investor. We ask that you disable ad blocking while on Silicon Investor in the best interests of our community. If you are not using an ad blocker but are still receiving this message, make sure your browser's tracking protection is set to the 'standard' level.

Biotech / Medical : Indications -- Psoriasis/Chronic Inflammation

Public Reply Prvt Reply Mark as Last Read File

Previous 10 Next 10 Previous Next

To: Icebrg who wrote (406)	6/14/2003 1:07:13 PM
From: scaram(o)uche	Read Replies (1) of 631

>> Now we need the help from Rick << Finally getting around to catching up with this thread. I'm about 30 messages behind....... Dose response issues..... first, I'd say that biopsy-negative data is sparse, and that we shouldn't worry too much about the inverse dose response. The story is still "way out". We also don't know if anti-integrin is merely passively covering an epitope that is critical to migration or inducing a CHANGE in the lymphocyte which reduces its capacity to migrate. (please correct me if data relevant to this issue is "out there" and conclusive, I'm behind.) Lack of dose response..... there are two different ways to look at "saturation" binding. One is when all available (or nearly) antigen on the cell is bound by antibody. Theoretically, this can occur for integrins at a molar ratio of 0.5, MAb:integrin. Under these conditions, cross linking occurs.......... one antibody can bind to two integrin molecules. As you increase the concentration of antibody, you increase the frequency with which one Fab is bound to integrin and the other is free. Under these conditions, integrin cross-linking is lower but "antigen saturation" is still complete. If the mechanism of action for the MAb is merely to passively cover the migration-relevant integrin, then you would not expect a bell-shaped dose response curve. If cross-linking is required to "change" the lymphocyte via integrin-mediated signaling, then higher doses of MAb will be less effective than some lower ones. Remember..... the ligands are on a cell surface are effectively immobilized relative to a soluble MAb. The immobilized ligand can act like an antibody to bring intracellular domains of integrins into proximity. Who would one ask to get a better grip on this sort of stuff, apart (perhaps) from (some) senior scientists at BGEN, ELN and MLNM? Jeff Ledbetter........... seattletimes.nwsource.com Ed Clark.......... ncbi.nlm.nih.gov These are two guys who think correctly. BTW, do you know Anders Orn at Karolinska, an old friend?

Report TOU Violation

Share This Post

Public Reply Prvt Reply Mark as Last Read File

Previous 10 Next 10 Previous Next