PMC:4939752 / 5103-6790 JSONTXT

{"project":"2_test","denotations":[{"id":"27413424-18469827-56394007","span":{"begin":415,"end":416},"obj":"18469827"},{"id":"27413424-18469827-56394007","span":{"begin":415,"end":416},"obj":"18469827"},{"id":"27413424-1172191-56394008","span":{"begin":512,"end":513},"obj":"1172191"},{"id":"27413424-1172191-56394008","span":{"begin":512,"end":513},"obj":"1172191"},{"id":"27413424-9704735-56394009","span":{"begin":877,"end":878},"obj":"9704735"},{"id":"27413424-9704735-56394009","span":{"begin":877,"end":878},"obj":"9704735"},{"id":"27413424-11579112-56394010","span":{"begin":1569,"end":1570},"obj":"11579112"},{"id":"27413424-11579112-56394010","span":{"begin":1569,"end":1570},"obj":"11579112"},{"id":"27413424-15613695-56394011","span":{"begin":1571,"end":1573},"obj":"15613695"},{"id":"27413424-15613695-56394011","span":{"begin":1571,"end":1573},"obj":"15613695"},{"id":"T20687","span":{"begin":415,"end":416},"obj":"18469827"},{"id":"T63086","span":{"begin":415,"end":416},"obj":"18469827"},{"id":"T11555","span":{"begin":512,"end":513},"obj":"1172191"},{"id":"T83186","span":{"begin":512,"end":513},"obj":"1172191"},{"id":"T53756","span":{"begin":877,"end":878},"obj":"9704735"},{"id":"T98010","span":{"begin":877,"end":878},"obj":"9704735"},{"id":"T85773","span":{"begin":1569,"end":1570},"obj":"11579112"},{"id":"T57508","span":{"begin":1569,"end":1570},"obj":"11579112"},{"id":"T11737","span":{"begin":1571,"end":1573},"obj":"15613695"},{"id":"T19240","span":{"begin":1571,"end":1573},"obj":"15613695"}],"text":"The concept of targeted immunotherapy was known almost a century before. Paul Ehrlich (1854–1915) the founder of immunology discovered a ‘magic bullet’ on the surface of an infected cell which able to selectively deliver a toxin to the bacterium inside the cell while sparing other tissues. This led to a discovery of therapy for syphilis in the pre-penicillin era for which Ehrlich received a Nobel Prize in 1908 [6]. The concept of the ‘magic bullet’ was successfully exploited by Milstein and Kohler in 1975 [7]. He successfully produced monoclonal antibodies using hybridoma technology and got Novel Prize for their intense scientific work. After two decades the concept of a ‘therapeutic magic bullet’ for cancer therapy was exist in 1997 with the approval of rituximab (anti-CD20 chimeric monoclonal antibody) by the US FDA for relapsed and refractory indolent lymphoma [8]. This was the first achievement of immunotherapy to kill B-lymphocytes by the use of anti-CD20 monoclonal antibody against the B-cell specific human CD20 cells surface molecules. The parallel successes of rituximab two other CD20 mAbs (Zevalin and Bexxar) were conjugated with radio-active materials to boost their therapeutic responses. Ibritumomab tiuxetan (Zevalin) is a CD20 mAb coupled with the radioactive isotope yttrium-90 or indium-111. Tositumumab (Bexxar) labeled with iodine-131. Both antibodies were approved by US FDA in 2002 and 2003 respectively. These are widely used for the treatment of follicular lymphoma (FL) patients and other NHLs as a part of radio-immunotherapy [9,10]. After that various mAbs have been raised against CD20 some of them have been approved for human use (Figure 1)."}