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Campath

Alemtuzumab (marketed as Campath or Campath-1H) is a monoclonal antibody used in the treatment of chronic lymphocytic leukemia (CLL) and T-cell lymphoma. more...

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Alemtuzumab targets CD52, a protein present on the surface of mature lymphocytes, but not on the stem cells from which these lymphocytes were derived. It is used as second line therapy for CLL. It was approved by the FDA for patients who have been treated with alkylating agents and who have failed fludarabine therapy.

A significant complication of therapy with alemtuzumab is that it significantly increses the risk for opportunistic infections, in particular, reactivation of cytomegalovirus.

Alemtuzumab is also used in some conditioning regimens for bone marrow transplantation.

History

The origins of alemtuzumab date back to Campath-1 which was derived from the mouse antibodies raised against human lymphocyte proteins (Hale et al 1983). The name "Campath" derives from the pathology department of Cambridge University. Initially, Campath-1 was unsuitable for therapy because patients reacted against the foreign mouse protein of the antibody. To circumvent this problem, Greg Winter and his colleagues humanised Campath-1, by extracting the hypervariable loops that had specificity for CD52 and grafted it onto a human antibody framework. This became known as Campath-1H and serves as the basis for alemtuzumab (Riechmann et al 1988).

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Campath Cleared for Marketing
From Applied Genetics News, 5/1/01

The U.S. Food and Drug Administration (FDA) has cleared Campath (alemtuzumab), ahumanized monoclonal antibody, for marketing as a treatment for patients with B-cell chronic lymphocytic leukemia (B-CLL) who have been treated with alkylating agents and have failed fludarabine therapy. Campath for B-CLL was developed by M&I Partners, a 50-50 joint venture of Millennium Pharmaceuticals, Inc. (640 Memorial Dr., Cambridge, MA 02139; Tel: 617/679-7000, Fax: 617/374-9379; Website: www.mlnm.com), and ILEX Oncology, Inc. (11550 I.H. 10 West, Suite 100, San Antonio, TX 78230; Tel: 210/949-8200, Fax: 210/949-8210; Website: www.ilexoncology.com) and will be marketed and distributed in the United States by Berlex Laboratories, Inc. (Montville, NJ).

Chronic lymphocytic leukemia is the most prevalent form of adult leukemia, affecting approximately 120,000 patients in the United States and Europe. B-CLL is characterized by an accumulation of leukemic (malignant) lymphocytes in the bone marrow, blood, and other tissues. As a result of the accumulation of malignant lymphocytes, bone marrow dysfunction and enlargement of the lymph nodes, liver, and spleen may occur.

Campath binds to CD52+, an antigen that is present on the surface of certain leukemic lymphocytes, and induces antibody-dependent lysis (killing) following binding. This results in the removal of the malignant lymphocytes from the blood, bone marrow, and other affected organs. In responders, treatment with Campath may improve blood counts and decrease the size of the liver and spleen. However, CD52 is also present on normal lymphocytes and other white blood cells.

"This represents a milestone in advancing Millennium's downstream capabilities through strategic partnerships that focus on the development of innovative products directed at unmet medical needs," says Mark Levin, CEO of Millennium.

"Monoclonal antibodies are powerful agents in the fight against cancer, and Campath is the first humanized monoclonal antibody indicated for the treatment of B-CLL and will provide a new option for patients who have failed standard therapies," comments Richard L. Love, president and CEO of Ilex.

Campath will be the first marketed drug for both Ilex and Millennium. Campath will be available for patients by early June.

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