Monoclonal antibody therapy rituximab

Monoclonal antibody therapy rituximab, alemtuzumab Non-specific immunotherapies and adjuvants BCG, interleukin-2 (IL-2), and interferon-a Immunomodulating drugs thalidomide and lenalidomide Cancer vaccines vaccine for advanced prostate cancer Side effects Flu-like symptoms, including fever, chills, nausea, and loss of appetite, allergic reactions, fatigue decrease in blood pressure Work better for some types of cancer than for others... 

McLaughlin P, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma Half of patients respond to a four dose treatment program. J Clin Oncol 1998 16 2825-2833. 

Bonner, J.A. et al., Cetuximab prolongs survival in patients with locoregionally advanced squamous cell carcinoma of head and neck a phase III study of high dose radiation therapy with or without cetuximab, Proc. Am. Soc. Clin. Oncol., 22, 489S, Abstr. 5507, 2004. McLaughlin, R et al., Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma half of patients respond to a four-dose treatment program, /. Clin. Oncol., 16, 2825-2833, 1998. 

Maloney, D.G., Grillo-Lopez, A.J., White, C.A., Bodkin, D., Schilder, R.J., Neidhart, J.A., Janakiraman, N., Foon, K.A., Liles, T.-M., Dallaire, B.K., Wey K., Royston, I., Davis, T., and Levy, R., IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin s lymphoma. Blood, 90, 2188-2195, 1997. 

Tobinai, K., RituxiMAb and other emerging monoclonal antibody therapies for lymphoma. Exp. Opin. Emerging Drugs 2002, 7(2), 289-302. 

Rituximab, a chimeric monoclonal antibody directed at the CD20 molecule on B cells, has become one of the most widely used therapies for follicular lymphoma. Rituximab is approved for first-line therapy either alone or combined with chemotherapy and as maintenance therapy for patients with stable disease or with partial or complete response following induction chemotherapy. 

Hainsworth, J.D., Burris III, H.A., Morrissey, L.H., Litchy S., Scullin, D.C., Jr., Bearden III, J.D., Richards, R, and Greco, RA., Rituximab monoclonal antibody as initial systemic therapy for patients with low-grade non-Hodgkin s lymphoma. Blood, 95, 3052-3056, 2000. 

Tositumomab is another anti-CD20 monoclonal antibody and is complexed with iodine 131 (131I). Tositumomab is used in two-step therapy in patients with CD20-positive, follicular non-Hodgkin s lymphoma whose disease is refractory to rituximab and standard chemotherapy. Toxicities are similar to those for ibritumomab and include severe cytopenias such as thrombocytopenia and neutropenia. Tositumomab should not be administered to patients with greater than 25% bone marrow involvement. 

Combination chemotherapy is the treatment standard for patients with diffuse non-Hodgkin s lymphoma. The anthracycline-containing regimen CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) has been considered the best treatment in terms of initial therapy. Recently, randomized phase III clinical studies have shown that the combination of CHOP with the anti-CD20 monoclonal antibody rituximab results in improved response rates, disease-free survival, and overall survival compared with CHOP chemotherapy alone. 

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. 

Colombat P, Salles G, Brousse N, et al. Rituximab (anti-CD20 monoclonal antibody) as single first-line therapy for patients with follicular lymphoma with a low tumor burden clinical and molecular evaluation. Blood 2001 97 101-106. 

Fludarabine is now being used as first-line therapy in younger patients, either alone or combined with cyclophosphamide or monoclonal antibodies (rituximab). 

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. 

Chimeric antibodies can be expressed in mammalian cells by introducing the recombinant DNA that codes for the antibody into the cells and selecting for the rare cell that has integrated the DNA into its own chromosomes and then expresses a new protein — the desired antibody. Additional genetic manipulations of the mammalian cells are then required to select cells that secrete large amounts of the recombinant protein. Following this research and development model would theoretically lead to successful monoclonal therapies, but in practice, it had never been accomplished before the IDEC team developed rituximab. 

---