immunology allergic disorders
Immunotherapeutics
Monoclonal antibodies
Monoclonal antibodies (mAbs) are manufactured in vitro to recognize specific targeted antigens (Ags); they are used to treat solid and hematopoietic tumors, inflammatory disorders, and infections. Most mAbs in clinical use target a single Ag, but a few are engineered to be bispecific. The monoclonal antibodies that are currently in clinical use include Murine Chimeric Humanized Fully human are produced by injecting a mouse with an antigen, harvesting its spleen to obtain B cells that are producing antibody specific to that antigen, fusing those cells with immortal mouse myeloma cells, growing these hybridoma cells (eg, in cell culture), and harvesting the antibody. Although mouse antibodies are similar to human antibodies, clinical use of murine monoclonal antibodies is limited because they induce human anti-mouse antibody production, can cause immune complex serum sickness (a type III Classification of Hypersensitivity Reactions ), and are rapidly cleared. To minimize the problems due to use of pure mouse antibody, researchers have used recombinant DNA techniques to create monoclonal antibodies that are part human and part mouse. Depending on the proportion of the antibody molecule that is human, the resultant product is termed one of the following: Chimeric Humanized In both cases, the process usually begins as above with production of mouse hybridoma cells that make antibody to the desired antigen. Then the DNA for some or all of the variable portion of the mouse antibody is merged with DNA for human immunoglobulin. The resultant DNA is placed in a mammalian cell culture, which then expresses the resultant gene, producing the desired antibody. If the mouse gene for the whole variable region is spliced next to the human constant region, the product is termed "chimeric." If the mouse gene for only the antigen-binding hypervariable regions of the variable region is used, the product is termed "humanized." Chimeric monoclonal antibodiesactivate antigen-presenting cells (APCs) and T cells more effectively than murine monoclonal antibodies but can still induce production of human anti-chimeric antibodies. against various antigens are available for the treatment of Colorectal Cancer , Fully human monoclonal antibodiesare produced using transgenic mice that contain human immunoglobulin genes or using phage display (ie, a bacteriophage-based cloning method) of immunoglobulin genes isolated from human B cells. Fully human monoclonal antibodies have decreased immunogenicity and therefore may have fewer adverse effects in patients. Monoclonal antibodies that target checkpoint molecules on either T cells or tumor cells (termed checkpoint inhibitors—see table Some Immunotherapeutic Agents in Clinical Use ) are used to prevent downregulation of antitumor responses and effectively treat some heretofore resistant cancers. However, because checkpoint molecules are also involved in other types of immune response, checkpoint inhibitors can cause severe immune-related inflammatory and autoimmune reactions (both systemic and organ specific). 