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

To: Icebrg who wrote (4239)	11/28/2001 8:03:19 AM
From: Icebrg	Read Replies (1) \| Respond to of 5665

Found the following on the net. Seems at least to be the right target. Antibodies specific for CD44 variant exon 6:candidates for immunotherapy of human tumors Heider K-H ( Boehringer Ingelheim Research and Development ) ?@Within the last few years, a new family of tumor-associated antigens, called CD44 variants or CD44 isoforms, has been characterized. CD44, a membrane bound glycoprotein, was originally described as a leucocyte antigen. With the detection of extensive alternative splicing and various types of post-translational modification, the definition of its molecular functions has become complex. Current evidence suugests that CD44 isoforms can function as adhesion molecules, in signal transduction, in cell migration and as tumor metastasis-promoting proteins . ?@One particular group of CD44 isoforms, namely those which contain the variant exon v6 (CD44v6), attracted closer attention among oncologists for several reasons. Firstly, v6 containing CD44 isoforms can confer metastatic potential to originally nonmetastasizing tumor cells, and secondly, antibodies against CD44v6 can prevent outgrowth of metastases in a syngeneic rat model. In humans, overexpression of exon v6 containing CD44 isoforms correlates with reduced patient survival in human breast and colon cancer and in non-HodgkinÕs lymphomas. ?@A murine monoclonal antibody to human CD44v6, BIWA 1 (clone VFF18), was selected due to its high-affinity binding to human tumor cells. Immunohistochemical analysis of more than 500 samples of different tumor types (breast, colon, head+neck, kidney, lung, prostate, stomach) revealed high levels of CD44v6 expression in breast carcinomas and squamous cell carcinomas (SCC). Detailed analysis of more than 200 cases of SCC (lung, head+neck, skin) confirmed expression of CD44v6 in 98% of the tumors. Analysis of non-malignant tissues revealed binding to a subset of epithelial tissues but no binding to non-epithelial tissues. ?@In a series of pre-clinical in vivo experiments in xenografted nude mice the tumor targeting properties of BIWA 1 were evaluated. Selective and dose-dependant uptake of BIWA 1 with a maximum of 18% ID/g tissue into A-431 human SCC xenografts was observed. The outcome of those experiments prompted us to initiate a clinical phase I study in 12 patients with advanced squamous cell carcinomas of the head and neck to detemine the targeting properties of BIWA 1 in tumor patients. takara.co.jp