Chronic lymphocytic leukemia monoclonal antibodies

This is a humanized anti-CD52 monoclonal antibody. At present it is in clinical use after bone marrow transplantation and for the treatment of refractory chronic lymphocytic leukemia. 

TGN1412 (CD28-SuperMAb) is a humanized monoclonal antibody that binds and acts as an agonist for the CD28 receptor of the immune system s T cell. It is intended to treat B cell chronic lymphocytic leukemia (B-CLL) and rheumatoid arthritis. 

Alemtuzumab is a recombinant DNA-derived humanized monoclonal antibody used in the treatment of chronic lymphocytic leukemia and T-cell lymphoma. It targets CD52, a protein present on the surface of mature lymphocytes. Alemtuzumab has been associated with infusion-related events including hypotension, rigors, fever, shortness of breath, bron-chospasm, chills, and/or rash. Also reported were syncope, pulmonary infiltrates, cardiac arrhythmias, myocardial infarction and cardiac arrest. 

This chapter reviews our current understanding of the mechanism of action of monoclonal antibody (especially rituximab), as well as the role of Fey receptor and Fey receptor gene polymorphisms, and their impact on treatment outcomes in hematologic malignancies including follicular lymphoma (FL), diffuse large B-cell lymphoma (DL-BCL), Waldenstrom s macroglobulinemia (WM), and chronic lymphocytic leukemia (CLL). 

Winkler U, Jensen M, Manzke O, Schulz H, Diehl V, Engert A. Cytokine-release syndrome in patients with B-cell chronic lymphocytic leukemia and high lymphocyte counts after treatment with an anti-CD20 monoclonal antibody (rituximab, IDEC-C2B8). Blood 1999 94(7) 2217-24. 

Alemtuzumab (campath-lH) is a humanized monoclonal antibody specific for the CDw52 antigen, present on cell membranes of lymphocytes and monocytes. It has been used for treatment of patients with rheumatoid arthritis and vasculitis, is being investigated for the treatment of chronic lymphocytic leukemia, and has been used to deplete circulating lymphocytes in patients with multiple sclerosis (1). In 2001, alemtuzumab was approved in Europe for the treatment of chronic B cell lymphocytic leukemia that had been treated previously with alkylating agents and was refractory to fludarabine (2). It has also been used for induction of immunosuppression/tolerance in liver transplant recipients (3,4) and kidney/pancreas transplant recipients (5). 

Cavalli-Bjorkman N, Osby E, Lundin J, Kalin M, Osterborg A, Gruber A. Fatal adenovirus infection during alemtuzumab (anti-CD52 monoclonal antibody) treatment of a patient with fludarabine-refractory B cell chronic lymphocytic leukemia. Med Oncol 2002 19(4) 277-80. 

ANLL, acute nonlymphocytic leukemia APE, acute promyelocytic leukemia CEL, chronic lymphocytic leukemia CML, chronic myelogenous leukemia EGER, epidermal growth factor receptor CIST, gastrointestinal stromal tumor MoAB, monoclonal antibody NE-kB, nuclear factor-KB Ph+ ALL, Philadelphia chromosome-positive acute lymphocytic leukemia PCP, Pneumocystis carinii pneumonia WBC, white blood cell. 

Campath , alemtuzumab, a humanized monoclonal antibody used in the treatment of B-cell chronic lymphocytic leukemia. The campath-IH family of antibodies recognize an abundant glycoprotein on virtually all human lymphocytes. Campath (Millenium Pharm. Inc. and ILEX Oncology Inc.) was registered in the USA in 2001 [M. A. van Dijk, J. G. J. van den Winkel, Curr. Opin. Chem. Biol. 2001, 5, 368]. 

Dillman RO et al. Murine monoclonal antibody therapy in two patients with chronic lymphocytic leukemia. Blood 1982 59 1036-1045. 

Furman RR, Forero-Torres A, Shustov A, Drachman JG. A phase I study of dacetuzumab (SGN-40, a humanized anti-CD40 monoclonal antibody) in patients with chronic lymphocytic leukemia. Leuk Lymphoma 2010 51 228-35. 

Byrd JG, Kipps TJ, Flirm IW, Gooper M, Odenike O, Bendiske J, et al. Phase 1 study of the anti-CD40 humanized monoclonal antibody luca-tumumab (HGD122) in relapsed chronic lymphocytic leukemia. Leuk Lymphoma 2012 53(11) 2136 2. 

Cioca, D.P. and Kitano, K. (2002). Apoptosis induction by hypercross-linking of the surface antigen CD5 with anti-CD5 monoclonal antibodies in B cell chronic lymphocytic leukemia. Leukemia 16, 335-343. 

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