Alemtuzumab

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.

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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.^[1] 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.^[2]

References

1. ^ Hale G, Bright S, Chumbley G, Hoang T, Metcalf D, Munro AJ, Waldmann H. Removal of T cells from bone marrow for transplantation: a monoclonal antilymphocyte antibody that fixes human complement. Blood 1983;62:873-82. PMID 6349718.
2. ^ Riechmann L, Clark M, Waldmann H, Winter G. Reshaping human antibodies for therapy. Nature 1988;332:323-7. PMID 3127726.