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

To: keokalani'nui who wrote (16)	4/5/2001 3:34:11 PM
From: keokalani'nui	Respond to of 1840

Preclinical. Genentech. Isotype-Dependent Inhibition of Tumor Growth In Vivo by Monoclonal Antibodies to Death Receptor 4 Anan Chuntharapai, Kelly Dodge, Katharine Grimmer, Kurt Schroeder, Scot A. Marsters, Hartmut Koeppen§, Avi Ashkenazi and K. Jin Kim1, Departments of * Antibody Technology, Cell Biology and Technology, Molecular Oncology, and § Pathology, Genentech, South San Francisco, CA 94080 To explore an approach for death receptor targeting in cancer, we developed murine mAbs to human death receptor 4 (DR4). The mAb 4H6 (IgG1) competed with Apo2L/TNF-related apoptosis-inducing ligand (DR4’s ligand) for binding to DR4, whereas mAb 4G7 (IgG2a) did not. In vitro, both mAbs showed minimal intrinsic apoptosis-inducing activity, but each triggered potent apoptosis upon cross-linking. In a colon tumor nude mouse model in vivo, mAb 4H6 treatment without addition of exogenous linkers induced apoptosis in tumor cells and caused complete tumor regression, whereas mAb 4G7 partially inhibited tumor growth. An IgG2a isotype switch variant of mAb 4H6 was much less effective in vivo than the parent IgG1-4H6, despite similar binding affinities to DR4. The same conclusion was obtained by comparing other IgG1 and IgG2 mAbs to DR4 for their anti-tumor activities in vivo. Thus, the isotype of anti-DR4 mAb may be more important than DR4 binding affinity for tumor elimination in vivo. Anti-DR4 mAbs of the IgG1 isotype may provide a useful tool for investigating the therapeutic potential of death receptor targeting in cancer. --Wilder

To: keokalani'nui who wrote (16)	4/19/2001 9:27:39 PM
From: scaram(o)uche	Read Replies (1) \| Respond to of 1840

You enjoyed the last one, and there's the Seattle touch. It's fun sharing my background. Some will be turned off........ Approaching Biology From a Different Angle SCIENTIST AT WORK / Leroy Hood By ANDREW POLLACK Message 15677887 Proc Natl Acad Sci U S A 1982 Jun;79(11):3613-7 Specific recognition of the product of a transferred major histocompatibility complex gene by cytotoxic T lymphocytes. Woodward JG, Orn A, Harmon RC, Goodenow RS, Hood L, Frelinger JA. Nature 1982 Jun 3;297(5865):415-7 Product of a transferred H-2Ld gene acts as restriction element for LCMV-specific killer T cells. Orn A, Goodenow RS, Hood L, Brayton PR, Woodward JG, Harmon RC, Frelinger JA.