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Monoclonal
Antibodies
Genetically Engineered Antibodies
Abzymes
Myeloma proteins are examples of monoclonal antibodies. They are homogenous antibodies produced by a clone of plasma cells originating from a single plasma cell that has mutated to divide continuously in an unregulated fashion. Myelomas arise spontaneously in humans and animals; usually the antigen specificity of the antibody is unknown. Monoclonal antibodies of a desired specificity can be produced in the laboratory by making hybridomas. Monoclonal antibodies are desirable for many research, diagnostic, and therapeutic purposes because of their defined nature and specificity. They can be coupled with fluorescent dyes to label cells in vitro, with radioactive probes for imaging tumors in vivo, and with toxins to kill tumor cells.
Mouse monoclonal antibodies injected into humans, for example to kill tumor cells, induce an immune response (HAMA) to the mouse antibody which eliminates the therapeutic antibodies.
Genetically Engineered Antibodies
Immunologists have used genetic engineering to modify monoclonal antibodies. Fab or (Fab')2 fragments can be made to eliminate the more immunogenic Fc region from the monoclonal antibodies; this also reduces their serum half life.
Chimeric antibodies are produced by cells engineered with mouse VH and VL gene segments of the desired specificity spliced to human CH and CL gene segments. In some cases, monoclonal antibodies are further humanized by splicing mouse CDR with human framework and C region gene segments.
Fv antibody is engineered to contain only VH and VL transcribed as a single polypeptide. Toxin sequences replace the Fc region of antibody in engineered immunotoxins.
Heteroconjugates are made with H-L pairs from different antibodies. If an H-L specific for tumor antigen were disulfide bonded with an H-L specific for Tc CD8, the heteroconjugate could cross-link cytotoxic T cells with tumor cells and promote tumor cell lysis.
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