MAbs therapy chimeric antibodies

Infliximab (in FLICKS ih mab) is a chimeric IgGic monoclonal antibody composed of human and murine regions. The antibody binds specifically to human TNF-a, thereby neutralizing that cytokine. Infliximab has been approved for Crohn s disease for both fistulizing and non-fistula disease. [Note Increased levels of TNF-a are found in fecal samples of patients with Crohn s disease.] It is not approved for maintenance therapy beyond six weeks. Approval for the treatment of rheumatic arthritis in combination with methotrexate is anticipated in the near future. 

In the last 2-5 years, selected monoclonal antibodies have become a routine part of care for certain malignancies. Rituximab, a chimeric monoclonal antibody used against CD 20 positive B-cell non-Hodgkin s lymphoma, is now utilized in combination with the CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone). Trastuzu-mab, a humanized monoclonal antibody, is a weekly maintenance therapy for HER2neu-positive metastatic breast cancer patients. 

Hybridoma technology and advanced antibody engineering has led to the design of an increasing number of site-directed therapeutic agents for the treatment and prevention of transplant rejection, therapy in rheumatoid arthritis, treatment of non-Hodgkin s lymphoma, and other indications. These products (Table 6.9) are examples of murine, chimeric, and humanized MAbs, and they represent significant advances in pharmacotherapy. 

Over the past decade, a wide variety of antibody-based targeting molecules have been assessed for their potential application in cancer therapy [200]. Monoclonal antibodies (mAb) were the first and are still the preferred class of targeting molecules. Current developments of antibodies have been focused on chimeric, humanized, and fully humanized derivatives to decrease their immunogenicity. Some of these antibody-based drugs have already undergone clinical development and have been successfully translated into the clinical environment. Such examples include rituximab (Rituxan ), trastuzumab (Herceptin ), cetuximab (Erbitux ), and bevacizumab (Avastin ). Rituximab was approved by the FDA for treating B-cell lymphoma in 1997. 

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