Present experience with Campath-1H in organ transplantation and its potential use in pediatric recipients This review will summarize the history of the development of Campath-1H antibody, touch on the biology of CD52, summarize experience in solid organ transplantation in humans with Campath-1H antibodies, refer to its use in non- transplant applications including malignancy and autoimmune disease, and make some suggestions regarding its potential use in children needing organ transplants. The experience in children is very limited, so this review will serve largely as background material summarizing some of the lessons that have been learned to date. History of the Campath-1H antibody In 1980, at the Cambridge University in England, the team led by Herman Waldmann and inclu- ding Geoff Hale produced the first MAbs to CD52 generated in a rat. Twenty-one years later, a genetically engineered and humanized version known as Campath-1H became licensed as alemtuzumab in the United States and Europe. The FDA approved the drug for treatment of CLL, but the antibody has been used in many other disease states as well as in transplantation. The history of Campath-1H’s development has been summarized in review articles by Herman Waldmann and Geoff Hale (1, 2). Rats were immunized to human T cells and fusions per- formed to create monoclonal antibodies. A few human complement-fixing antibodies were detec- ted and most were later identified as reacting with CD52. One of these anti-CD52 complement- fixing antibodies with broad specificity was of a rat IgM isotype with the name of YTH66.9. The antibody was named Campath-1M and was shown by Shimon Slavin to prevent GVHD (3). However, although patients avoided GVHD, some rejected their marrow. It was subsequently learned that the target of Campath-1 antibodies were abundantly expressed on most lymphocytes, normal or malignant, and that these antibodies might have utility for in vivo use given their lytic potency. The rat IgG2b isotype was identified and became known as Campath-1G. In order to produce clinical grade antibodies, the TAC was founded and Campath-1G produced for application to CLL, GVHD, and bone marrow transplantation. Fortuitously, focus on a human Knechtle SJ. Present experience with Campath-1H in organ transplantation and its potential use in pediatric recipients. PediatrTransplantation2004:8:106–112. Ó 2004BlackwellMunksgaard Abstract: Campath-1H is a humanized monoclonal antibody directed at CD52 expressed on lymphocytes and other cells of the immune system. It has been tested extensively in lymphoid malignancies, autoimmune diseases including rheumatoid arthritis, multiple sclerosis, and organ transplantation. Although its use in children has been limited to date, so far it appears to be well tolerated in children. Currently, studies are being implemented to further assess its safety and efficacy in pediatric organ transplantation. Immune cell depletion using Campath-1H appears to be particularly useful in organ transplantation in that lower doses of maintenance immunosuppressive drugs are needed. This feature is particularly attractive in children. Stuart J. Knechtle Division of Transplantation, Department of Surgery, University of Wisconsin Medical School, Madison, WI, USA Key words: campath-1H – kidney transplantation – lymphocyte depletion Stuart J. Knechtle MD, Department of Surgery, University of Wisconsin Hospital and Clinics, 600 Highland Avenue, Madison, WI 53792-7375, USA Tel.: (608) 263-2527 Fax: (608) 262-6280 E-mail: stuart@surgery.wisc.edu Accepted for publication 9 October 2003 Abbreviations: ADCC, antibody-dependent cellular cyto- toxicity; Campath-1H, Cambridge Pathology 1 IgM isotype; CLL, chronic lymphocytic leukemia; CMV, cytomegalovi- rus; FDA, Food and Drug Administration; GVHD, graft vs. host disease; HLA, human leukocyte antigen; MAbs, monoclonal antibodies; MHC, major histocompatibility complex; MMF, mycophenolate mofetil; NIH, National Institutes of Health; NK, natural killer; TAC, Therapeutic Antibody Center. Pediatr Transplantation 2004: 8: 106–112 Printed in UK. All rights reserved Copyright Ó 2004 Blackwell Munksgaard Pediatric Transplantation 106