various environmental conditions, their therapeutic efficacy and their detectability in diagnostic applications. fermentation chambers have been used for large scale antibody production. chimeric antibodies while mouse and human antibodies are structurally similar, the differences between them were sufficient to invoke an immune response when murine monoclonal antibodies were injected into humans, resulting in their rapid removal from the blood, as well as systemic inflammatory effects and the production of human anti-mouse antibodies (hama). recombinant dna has been explored since the late 1980s to increase residence times. in one approach called "cdr grafting", mouse dna encoding the binding portion of a monoclonal antibody was merged with human antibody-producing dna in living cells. the expression of this "chimeric" or "humanised" dna through cell culture yielded part-mouse, part-human antibodies. human antibodies approaches have been developed to isolate human monoclonal antibodies. ever since the discovery that monoclonal antibodies could be generated, scientists have targeted the creation of fully human products to reduce the side effects of humanised or chimeric antibodies. several successful approaches have been identified: transgenic mice, phage display and single b cell cloning: cost monoclonal antibodies are more expensive to manufacture than small molecules due to the complex processes involved and the general size of the molecules, all in addition to the enormous research and development costs involved in bringing a new chemical entity to patients. they are priced to enable manufacturers to recoup the typically large investment costs, and where there are no price controls, such as the united states, prices can be higher if they provide great value. seven university of pittsburgh researchers concluded, "the annual price of mab therapies is about $100,000 higher in oncology and hematology than in other disease states", comparing them on a per patient basis, to those for cardiovascular or metabolic disorders, immunology, infectious diseases, allergy, and ophthalmology. applications diagnostic tests once monoclonal antibodies for a given substance have been produced, they can be used to detect the presence of this substance. proteins can be detected using the western blot and immuno dot blot tests. in immunohistochemistry, monoclonal antibodies can be used to detect antigens in fixed tissue sections, and similarly, immunofluorescence can be used to detect a substance in either frozen tissue section or live cells. analytic and chemical uses antibodies can also be used to purify their target compounds from mixtures, using the method of immunoprecipitation. therapeutic uses main article: monoclonal antibody therapy therapeutic monoclonal antibodies act through multiple mechanisms, such as blocking of targeted molecule functions, inducing apoptosis in cells which express the target, or by modulating signalling pathways. cancer treatment one possible treatment for cancer involves monoclonal antibodies that bind only to cancer-cell-specific antigens and induce an immune response against the target cancer cell. such mabs can be modified for delivery of a toxin, radioisotope, cytokine or other active conjugate or to design bispecific antibodies that can bind with their fab regions both to target antigen and to a conjugate or effector cell. every intact antibody can bind to cell receptors or other proteins with its fc region. monoclonal antibodies for cancer. adept, antibody directed enzyme prodrug therapy; adcc: antibody dependent cell-mediated cytotoxicity; cdc: complement-dependent cytotoxicity; mab: monoclonal antibody; scfv, single-chain fv fragment. mabs approved by the fda for cancer include: alemtuzumab bevacizumab cetuximab dostarlimab gemtuzumab ozogamicin ipilimumab nivolumab ofatumumab panitumumab pembrolizumab ranibizumab rituximab trastuzumab autoimmune diseases monoclonal antibodies used for autoimmune diseases include infliximab and adalimumab, which are effective in rheumatoid arthritis, crohn's disease, ulcerative colitis and ankylosing spondylitis by their ability to bind to and inhibit tnf-α. basiliximab and daclizumab inhibit il-2 on activated t cells and thereby help prevent acute rejection of kidney transplants. omalizumab inhibits human immunoglobulin e (ige) and is useful in treating moderate-to-severe allergic asthma. examples of therapeutic monoclonal antibodies for a more comprehensive list, see list of monoclonal antibodies.