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

To: Icebrg who wrote (697)	6/25/2003 12:35:08 PM
From: tuck	Respond to of 2240

Here's the abstract; doesn't add much . . . >>Published online before print June 25, 2003 Proc. Natl. Acad. Sci. USA, 10.1073/pnas.1533209100 Immunology Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma Giao Q. Phan , James C. Yang , Richard M. Sherry , Patrick Hwu , Suzanne L. Topalian , Douglas J. Schwartzentruber , Nicholas P. Restifo , Leah R. Haworth , Claudia A. Seipp , Linda J. Freezer , Kathleen E. Morton , Sharon A. Mavroukakis , Paul H. Duray , Seth M. Steinberg , James P. Allison ¶, Thomas A. Davis \|\|, and Steven A. Rosenberg Surgery Branch, Laboratory of Pathology, and Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; ¶Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720; and \|\|Medarex, Inc., Princeton, NJ 08540 Contributed by James P. Allison, May 27, 2003 Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a critical immunoregulatory molecule (expressed on activated T cells and a subset of regulatory T cells) capable of down-regulating T cell activation. Blockade of CTLA-4 has been shown in animal models to improve the effectiveness of cancer immunotherapy. We thus treated 14 patients with metastatic melanoma by using serial i.v. administration of a fully human anti-CTLA-4 antibody (MDX-010) in conjunction with s.c. vaccination with two modified HLA-A*0201-restricted peptides from the gp100 melanoma-associated antigen, gp100:209-217(210M) and gp100:280-288(288V). This blockade of CTLA-4 induced grade III/IV autoimmune manifestations in six patients (43%), including dermatitis, enterocolitis, hepatitis, and hypophysitis, and mediated objective cancer regression in three patients (21%; two complete and one partial responses). This study establishes CTLA-4 as an important molecule regulating tolerance to "self" antigens in humans and suggests a role for CTLA-4 blockade in breaking tolerance to human cancer antigens for cancer immunotherapy.<< Cheers, Tuck

To: Icebrg who wrote (697)	6/25/2003 12:38:57 PM
From: Icebrg	Read Replies (1) \| Respond to of 2240

The article is available (at a cost of 10 USD) on the net. What is not clear from the PR is that the study was stopped after 14 patients had been recruited due to grade III/IV autoimmune side-effects. The original recruitment target was 21 participants. Nothing about that in the PR. Instead they wrote: In the initial cohort of 14 patients with metastatic disease as if 14 had indeed been the intended enrollment target. Well, it wasn't. The study will now continue in a second phase. I suppose that they will have to reduce the dosage used in the first phase. Erik