I remember the day, many moons ago, when SGEN IPO'd, that you said to treat it roughly. If BLUE HP thought it could have shorted it, it would have, and made money.
Now, I wonder if it isn't emerging as a sleeper antibody company. It's inclusion in Biotech Jim's '04 Charity portfolio must mean something positive. As perhaps, does the fact that it was you who started this thread. What are you guys seeing here now? Do they have the best armed antibody technology?
Is Senter still with the company?
>>Bioconjug Chem. 2003 Sep-Oct;14(5):927-33.
Conditionally cleavable radioimmunoconjugates: a novel approach for the release of radioisotopes from radioimmunoconjugates.
Beeson C, Butrynski JE, Hart MJ, Nourigat C, Matthews DC, Press OW, Senter PD, Bernstein ID.
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
One of the limitations of therapy with radiolabeled monoclonal antibodies (mAbs) is that significant toxicities can arise from circulating non-tumor-bound radiolabeled conjugate. Here, we describe a new method to reduce systemic radiation exposure from radiolabeled mAbs involving the attachment of the radioisotope through a linker that can be cleaved by an administered enzyme. To demonstrate the feasibility of this approach, we prepared a conditionally cleavable radioimmunoconjugate (RIC) composed of (131)I-labeled cephalosporin conjugated to Tositumomab, a mAb against the CD20 antigen. The cleavable RIC bound antigen identically to directly iodinated antibody, and in the presence of beta-lactamase, about 80-85% of the radioisotope was released. In vivo studies in mice revealed that the cleavable RIC and the directly iodinated anti-CD20 antibody had similar biodistribution patterns. Systemically administered beta-lactamase induced a 2-3-fold decrease in the percent injected dose (ID) of the cleavable RIC/g of blood, marrow, spleen, lung, and liver 1 h after enzyme treatment, and a 4-6-fold decrease 20 h after enzyme treatment. This was accompanied by a 20-fold increase in % ID/g in urine 1 h after enzyme treatment, indicating that the released radiolabel was rapidly excreted through the kidneys. In mice with human tumor xenografts, there was no decrease in the %ID/g in tumor 1 h after enzyme treatment, but by 4 h after enzyme injection, decreases in tumor radioactive content began to diminish the targeting advantage. These studies demonstrate that the cleavable RIC substrate is able to bind to tumor antigens and localize within human tumor xenografts and that accelerated systemic clearance can be induced with beta-lactamase.<<
Why is this published under the auspices of Fred Hutchinson? Does SGEN have a deal with them?
Mind you, I'm just coming in all of the sudden form left field. I know nothing, and appreciate any catching up you can do for me.
OT:
Good Chards recently:
Frank Family '01 (which was supposed to be a bad year for Napa chardonnays. Can you say butter? Get it under $20 bucks if you can.)
Under $5 -- at least at the discount store -- '02 Butterfield Station. Incredible butter for the price, at the cost of some balance in the fruit.
St. Francis '02 -- around $10. Not as big as the Frank Family, but almost, and pretty well balanced.
Same price point: Kendall Jackson Vintner's Reserve, almost as good. Ditto your state's Columbia Crest Grand Estates '02. Consistently good butter and value over several years, IMO.
That old Lembey Champagne? Almost flat but tasty. I hear some folks actually cellar high end champagnes for years, knowing they'll go flat, yielding a great still wine. Interesting concept. Restaurants in Arizona don't uncork wines from private collections, the silly bastards -- no wonder we Californians charge such high hotel taxes. Thus my sister still has the Carmenet, and maybe she'll save it for another dinner that I can attend.
Cheers (make mine a double), Tuck |
