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Biotech / Medical : MedImmune -- Ignore unavailable to you. Want to Upgrade?

To: Pseudo Biologist who wrote (148)	2/24/1999 1:04:00 AM
From: scaram(o)uche	Read Replies (1) \| Respond to of 416

PB: Yeah, not sexy sounding. However, there are lots of sexy or "special" anti-CD2s. It's just that all the others are agonists. :-) I agree with your sentiment/thoughts. However, I dare anyone to read Dumont et al. and walk away thinking anything other than either "wow!" or "drylab?". As you well know, the proposed mechanism of action is apoptosis in T cells that have specifically interacted with antigen. Would that be good enough? Wouldn't you say that the limited efforts initiated at MEDI are either (1) inconsistent with in vitro (remember, the epitope is only found on human, gorilla and chimp..... no monkeys) results that BTRN is proud to point at, or (2) indicative that subsequent work doesn't support those results? The alternative, the inescapable alternative, would be that management at MEDI is not capable of handling, at this time, a goldmine. If that's the case, then, quickly, let's let someone else develop the product. It does not seem wise to pursue GvH full-out and to merely poke around at psoriasis among autoimmune diseases. We need an explanation..... either 507 doesn't work as proposed, or MEDI is letting a $3 billion/year op slip away. I just looked for new papers, and didn't find anything beyond what we've already seen. I did find this, however, among older work...... Immunology 1997 Sep;92(1):39-44 A multimeric form of soluble recombinant sheep LFA-3 (CD58) inhibits human T-cell proliferation. Yamashita K, Parish CR, Warren HS, Harrison LC Kaneka Corporation, Takasago Research Laboratories, Hyogo, Japan. The rosetting of T cells by sheep erythrocytes is mediated through the interaction of the CD2 molecule on T cells with T11TS, a molecule on sheep erythrocytes homologous to lymphocyte function-associated antigen-3 (LFA-3, CD58). We cloned a T11TS cDNA from sheep leucocyte mRNA which encodes a soluble molecule comprising the distal D1 and the D2 extracellular domains, but not the transmembrane domain. cDNA for this soluble D1 + D2 form of sheep LFA-3 (sLFA-3) was expressed in Escherichia coli and the properties of the purified recombinant protein were assessed by inhibition of T-cell rosette formation. sLFA-3 inhibited rosette formation, but its activity was low, 50% inhibition occurring at 25 micrograms/ml, consistent with the observed low binding avidity of fluorescein isothiocyanate (FITC)-labelled sLFA-3, sLFA-3 was made multimeric to increase its affinity, by crosslinking biotinylated sLFA-3 to streptavidin-biotinylated dextran complexes. The binding of crosslinked sLFA-3 multimers, tested by fluorescence-activated cell sorting (FACS) analysis, was significantly increased compared to sLFA-3 monomers. Competition with monoclonal antibodies demonstrated that multimeric sLFA-3 bound to the T11(1) epitope on CD2. The multimeric form of sLFA-3 was significantly more potent than the monomer in inhibiting proliferation of human T cells in response to purified protein derivative (PPD), tetanus toxoid (TT) or allogeneic cells. Multimeric sLFA-3 might, therefore, have potential as an immunotherapeutic agent to inhibit and/or anergize antigen-specific T-cell responses.