Monoclonal Antibodies for Cancer Therapy

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The administration of recombinant monoclonal antibodies for cancer is based on the premise that tumor-specific antibodies can recognize and target cancer cells and, once in the tumor microenvironment, can inhibit tumor growth or induce tumor regression via mechanisms including antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) (2,3). The anti-CD20 monoclonal antibody rituximab, for example, binds to the B-cell antigen CD20 expressed on B-cell lymphomas to kill cancer cells via ADCC and induction of apoptosis (4-6). The monoclonal antibody trastuzumab binds to the receptor for the growth factor HER-2, which is overexpressed in up to 30% of human breast cancers, to block the proliferative effects of this growth factor on breast cancer cells (7). Monoclonal antibodies have also been conjugated to tumor-killing substances such as radioisotopes, drugs, or toxins (8-10). Although monoclonal antibody therapy has yielded positive results in some human cancers, it has several limitations. Shortcomings include poor penetration of solid masses with resulting impaired distribution of antibody at the tumor, heterogeneity of antigen expression leading to suboptimal monoclonal binding to tumor, and limited direct activation of tumor cell destruction (2).

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