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Biotech / Medical : MEDX ... anybody following? -- Ignore unavailable to you. Want to Upgrade?

To: tuck who wrote (658)	4/7/2003 6:51:37 PM
From: tuck	Respond to of 2240

From this year's scuttled AACR meeting: >>Abstract Number: 849 An Antigen Presenting Cell-Targeted Cancer Vaccine that Elicits CD4 and CD8 Effector Responses to the hCGb Tumor-Associated Antigen. Lizhen He, Venky Ramakrishna, John Treml, Xi-Tao Wang, Patti Smith, John Conolly, Paul Wallace, Tibor Keler, Michael Endres, Medarex, Inc., Bloomsbury, NJ; Dartmouth Medical School, Dartmouth, NH. Vaccines capable of raising potent cellular responses in addition to generating therapeutic antibodies may offer added therapeutic benefits in the treatment of cancer. Here we describe the development of an antigen presenting cell (APC)-targeted cancer vaccine capable of eliciting strong cellular immune responses directed against the hCG b subunit. Human chorionic gonadotropin is a heterodimeric hormone that is normally expressed during pregnancy. The hCG b subunit is also markedly over expressed by a number of carcinomas; including cancers of the colon, lung, pancreas, breast, bladder, and ovary. In order to increase immune responses to hCGb , we have coupled this tumor-associated antigen to a fully human monoclonal antibody (B11) that targets human dendritic cells and macrophages. Flow cytometry on living cells and immunohistochemical analysis on fixed frozen tissues indicate that like B11 antibody, B11-hCGb also binds to dendritic cells and macrophages. In addition, confocal microscopy analysis confirms that B11-hCGb is rapidly internalized by in vitro cultured monocyte-derived dendritic cells. Furthermore, monocyte-derived dendritic cells pulsed with B11-hCGb elicit potent cytolytic and proliferative T cell responses, more potent than dendritic cells pulsed with hCGb immune complexes. Addition of HLA I- and II-specific antibodies abrogates this T cell reactivity in both proliferation and cytotoxicity assays. Delivering hCGb tumor antigen to dendritic cells via a fully human antibody results in cross presentation of hCGb -derived antigens by accessing both the Class I and Class II pathways and offers potential for therapeutic intervention with respect to a number of cancers. << Cheers, Tuck