To print: Select File and then Print from your browser's menu --------------------------------------------------------------------------------------- Title: Drug Blocks Graft Versus Host Disease In Mismatched Bone Marrow Transplant URL: http://www.pslgroup.com/dg/1026FA.htm Doctor's Guide June 3, 1999
NEEDHAM, MA -- June 3, 1999 -- Results from a clinical trial of Repligen Corp.'s CTLA4-Ig in patients receiving a bone marrow transplant for the treatment of leukemia and other malignant and non-malignant diseases of the blood were published in today's edition of the New England Journal of Medicine. The drug was evaluated for its ability to block the development of graft versus host disease (GVHD), a condition in which the newly-transplanted marrow attacks the recipient or host. As reported in the Journal, researchers from the Dana-Farber Cancer Institute, Boston, performed bone marrow transplants on 12 patients who received marrow from a genetically mismatched family member. Mismatched family members are not generally eligible to be donors because of the expectation of a high incidence of severe and potentially life-threatening GVHD. The Dana-Farber investigators reported that following pre-treatment of donor bone marrow with CTLA4-Ig only three out of the 11 evaluable patients experienced acute GVHD and only one developed chronic GVHD following bone marrow transplantation. The observation of a reduced incidence of GVHD was supported by laboratory measurements which indicated that the immune reactivity of the transplanted marrow against the host was reduced, on average, by nearly 100-fold, or 99 percent. Furthermore, the immune suppression induced with CTLA4-Ig was specific for those T-cells involved in mediating GVHD indicating that potentially beneficial immune responses were left intact. This is in contrast to other approaches to blocking GVHD which employ non-specific immunosuppressants which can leave the patient vulnerable to infection. These data are the first demonstration in humans that CTLA4-Ig can specifically inactivate a targeted subset of the immune system. In the Journal report, the Dana-Farber investigators describe a treatment in which the donor's marrow was incubated ex vivo (outside the body) with CTLA4-Ig and an irradiated (inactivated) sample of blood cells from the recipient. After 36 hours the CTLA4-Ig was removed and the bone marrow, now treated to selectively block the T-cells most likely to cause GVHD, was infused into the patient. A bone marrow transplant is a potential cure for leukemia, as well as several diseases of the immune and hematopoietic system. Despite the clinical success of such transplants, a significant number of patients experience GVHD, making transplantation a high risk, life-threatening procedure. To minimise this complication, most bone marrow transplant candidates require an extensive search for a genetically matched donor, often delaying treatment for months. Even when an unrelated matched donor is identified, prophylaxis of GVHD with non specific immunosuppressive drugs or elimination of T-cells is necessary resulting in the loss of certain desirable activities of these disease-fighting cells. Furthermore, this process only partially eliminates the risk of GVHD. To date, GVHD has prevented the use of mismatched donors in bone marrow transplantation. CTLA4-Ig is a derivative of a natural immune cell protein (CTLA4), which has been shown to selectively turn off immune responses. CTLA4-Ig has been shown by numerous research groups to have activity in animal models of solid organ transplantation (heart and kidney), and suppression of autoimmune diseases such as lupus and multiple sclerosis. Related Links: New England Journal of Medicine --------------------------------------------------------------------------------------------- Copyright © 1999 P\S\L Consulting Group Inc. All rights reserved. Republication or redistribution of P\S\L content is expressly prohibited without the prior written consent of P\S\L. P\S\L shall not be liable for any errors, omissions or delays in this content or any other content on its sites, newsletters or other publications, nor for any decisions or actions taken in reliance on such content. --------------------------------------------------------------------------------------------- This news story was printed from *Doctor's Guide to the Internet* located at http://www.docguide.com --------------------------------------------------------------------------------------- Return to News Story Page This site is maintained by webmaster@pslgroup.com Please contact us with any comments, problems or bugs. All contents Copyright (c) 1998 P\S\L Consulting Group Inc. All rights reserved.