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Biotech / Medical : IDPH--Positive preliminary results for pivotal trial of ID -- Ignore unavailable to you. Want to Upgrade?

To: Webhead who wrote (1613)	10/30/1998 4:10:00 AM
From: Maurice Winn	1 Recommendation Read Replies (1) \| Respond to of 1762

Ed, a lymphoma specialist at Scripps Clinic told me in February that the mechanism of action by Rituxan against NHL was unclear. Overall he seemed to have a doubtful view as to its efficacy, saying that he can shrink tumors by half with steroids so wasn't too impressed by some of the response rates of tumors. So the mechanism is not simply a matter of cell identification. Thanks for the half-life explanation for CD20 and that you don't think Rituxan would coat cancer cells and thereby harden them against subsequent Y2B8 treatment. Rituxan doesn't fail in some people. It fails in most people. In as much as not many people are "cured" with no recurrence. Even in tumor suppression the number of complete responses is, to me anyway, not that great. I suppose the failure is because not all cancer cells in a tumor are exposed to the Rituxan, because they are buried inside the tumor with no blood supply. Also, there is, I suppose, a wide variation on the degree of expression of CD20. Meanwhile, the stock jumped $3! Maurice

To: Webhead who wrote (1613)	10/30/1998 8:29:00 PM
From: DMB	1 Recommendation Read Replies (1) \| Respond to of 1762

Re: "I ran a quick literature search to try and find out how Rituxan actually kills the lymphoma cells. All I found was that some cells die by complement activation (where the immune system attacks and causes the rupture of the target cell) and others by other means. In other words, not very informative! Perhaps someone more familiar with Rituxan's mode of action could chime in here." I saw a presentation about a year ago where several antibodies were compared in an in vitro cell lysis assay (a test tube experiment on cell killing). All 5 antibodies were monoclonals directed at a specific 5 aminoacid portion of the CD20 molecule. One of the antibodies was Rituxan (another was the Coulter anti-B1 antibody). Only the Rituxan produced cell lysis in this assay. How to interpret this observation? Beats me, but I would think that it is not likely an "immune" effect or a "complement" mediated effect. Makes me wonder if Rituxan is acting by affecting a signalling pathway of some sort.