Monoclonal antibodies

Monoclonal antibodies

Recombinant DNA technology has allowed for the development of monoclonal antibodies directed at such targets as other immunecells or cancer cells. Monoclonal antibodies include:

·                 alemtuzumab

·                 gemtuzumab ozogamicin

·                 ibritumomab tiuxetan

·                 rituximab

·                 trastuzumab.

Pharmacokinetics

Because of their large protein molecule structure, monoclonal an-tibodies aren’t absorbed orally. They may have a limited distribu-tion as well as a long half-life, sometimes measured in weeks.

Pharmacodynamics

Monoclonal antibodies bind to target receptors or cancer cells and cause tumor death via several mechanisms: They may induce pro-grammed cell death; they may recruit other elements of the im-mune system to attack the cancer cell; or they may deliver a dose of a toxic chemotherapy drug (gemtuzumab) or radiation (ibritu-momab) to the tumor site.

Pharmacotherapeutics

Monoclonal antibodies have demonstrated activity in both solid tumors and hematologic malignancies, such as:

§    non-Hodgkin’s lymphoma—rituximab and ibritumomab (target CD20 or malignant B lymphocytes)

§    chronic lymphocytic leukemia—alemtuzumab (target CD52 antigen or B cells)

§    acute myeloid leukemia—gemtuzumab (target CD33 antigen in myeloid leukemic cells)

§    breast cancer—trastuzumab (target HER-2 protein in breast cancer cells).

Drug interactions

Although no interactions have been noted with alemtuzumab, mul-tiple drug interactions are associated with other monoclonal anti-bodies.

·               Ibritumomab may interfere with the actions of such drugs as warfarin, aspirin, clopidogrel, ticlopidine, nonsteroidal anti-inflammatory drugs, azathioprine, cyclosporine, and corticoste-roids.

·                 Trastuzumab increases the cardiac toxicity associated with an-thracycline administration. (See Adverse reactions to monoclonalantibodies.)