A personal history of the CAMPATH-1H antibody.
The recent licensing of CAMPATH-1H (alemtuzumab) for the treatment of patients with refractory chronic lymphocytic leukemia has been the culmination of a long journey. This success is in large part due to the persistence, dedication, and commitment of a large number of academic collaborators. The first breakthrough was the identification of CAMPATH-1M, an isotype directed against CD52, and extremely efficient at lysing target cells in the presence of human complement, but limited in vivo by the rate of complement biosynthesis. The search for a monoclonal antibody that was more efficient in vivo found the rare class-switching variant CAMPATH-1G, which is able to kill target cells by antibody-dependent cell-mediated cytotoxicity. Construction of the humanized form of the antibody, CAMPATH-1H, and the development of resources to manufacture clinical-grade material, further expedited many studies across the world in leukemia and lymphoma as well as in marrow transplantation, autoimmune disorders, and kidney transplantation. Such studies have taught us a lot about the diseases themselves, as well as offering the prospect of harnessing immunological tolerance processes to facilitate a whole new approach to immunosuppression.
Sir William Dunn School of Pathology, Oxford. herman.waldmann@path.ox.ac.uk
Herman
H
Waldmann
D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000302:isolation & purification / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000302:isolation & purification / Q000627:therapeutic use*; D015703:Antigens, CD / Q000187:drug effects*; D000951:Antigens, Neoplasm / Q000187:drug effects*; D016026:Bone Marrow Transplantation / Q000276:immunology; D000074301:CD52 Antigen; D006023:Glycoproteins / Q000187:drug effects*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D000074323:Alemtuzumab