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

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 Food and Drug Administration 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
increases the risk for opportunistic infections, in particular, reactivation
of cytomegalovirus.

Alemtuzumab is also used in some conditioning regimens for bone
marrow transplantation and kidney transplantation. It is also used under
Clinical Trial protocols for treatment of some autoimmune diseases, such
as Multiple Sclerosis.

Description

Alemtuzumab is a recombinant DNA-derived humanized monoclonal
antibody (Campath-1H) that is directed against the 21-28 kD cell surface
glycoprotein, CD52.

Indications and Use

Alemtuzumab is indicated for the treatment of B-cell chronic lymphocytic
leukemia (B-CLL) in patients who have been treated with alkylating agents
and who have failed fludarabine therapy.

Contraindications and Precautions

Alemtuzumab is contraindicated in patients who have active systemic
infections, underlying immunodeficiency (e.g., seropositive for HIV),
or known Type I hypersensitivity or anaphylactic reactions to Campath
or to any one of its components.

Adverse Reactions

Alemtuzumab has been associated with infusion-related events including
hypotension, rigors, fever, shortness of breath, bronchospasm, chills,
and/or rash. In post-marketing reports, the following serious infusion-related
events were reported: syncope, pulmonary infiltrates, ARDS, respiratory
arrest, cardiac arrhythmias, myocardial infarction and cardiac arrest.
The cardiac adverse events have resulted in death in some cases.

History

The origins of alemtuzumab date back to Campath-1 which was derived from
the mouse antibodies raised against human lymphocyte proteins by Herman
Waldmann and colleagues (Hale et al 1983). The name “Campath”
derives from the pathology department of Cambridge University. Initially,
Campath-1 was not ideal for therapy because patients could, in theory,
react against the foreign rat protein determinants 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).