Immunotherapy chimeric antibodies

J. Newman, J. Albert, D. Anderson, K. Carner, C. Heard, F. Norton, R. Raab, M. Reff, S. Shuey, and N. Hanna, Primatization of recombinant antibodies for immunotherapy of human diseases A macaque/human chimeric antibody against human CD4, Biotechnology, 10, 1455 (1992). 

Monoclonal antibodies may be used as passive immunotherapy to treat malignancies. They react with specific antigens present on the surface of tumor cells and result in cell destruction. Rituximab was the first MoAb approved in the United States for the treatment of cancer. It is a chimeric MoAb directed against cluster differentiation 20 (CD20) markers, which are expressed on over 90% of B-cell NHL tumors. Rituximab is thought to result in B-cell depletion by a number of mechanisms, including complement-mediated and antibody-dependent cell lysis and induction of apoptosis. 

Steffens MG, Boerman OG, de Muldet PH, et al. Phase I tadio-immunotherapy of metastatic tenal cell carcinoma with 1311-labeled chimeric monoclonal antibody G250. Clin Cancer Res. 1999 5 3268s. 

The extracellular domain of the HER-2 neu molecule is the therapeutic target for the specific IgGlx humanized chimeric monoclonal antibody Trastuzumab (Herceptin ), approved 1998 and found to be effective in malignancies with HER-2 overexpression. An important aspect of this specific immunotherapy includes the efficiency against non-proliferating disseminated tumor cells (dormant cells), which are usually in the GO phase of the cell cycle, where conventional chemotherapy is less effective. The HER-2 neu molecule is also the target for specific tyrosine kinase inhibitors such as Tykerb (lapatinib ditosylate), which block the kinase-substrate interaction and the extracellular tyrosine kinase receptors on tumor cells. 

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