Delivery and Effector Function of Antibody Therapeutics in Human Solid Tumor
INTRODUCTION In the 2000s, therapeutic antibodies have been shown to improve overall survival as well as time to disease progression in a variety of human malignancies such as breast, colon, and hematological cancers. In 1980s, the administration of nonhuman therapeutic antibodies, such as mouse monoclonal immunoglobulin, caused a severe host immune response, referred to as the human antimouse antibody (HAMA) response, which resulted in the prompt elimination of the administered therapeutics as a foreign substance from human patients before a sufficient therapeutic effect was achieved. Recent progress in antibody engineering technology has overcome this major problem of immunogenicity. Mouse/human chimeric and complementarity-determining region (CDR)- grafted antibodies have been generated as humanized antibodies, and fully humanized antibodies have also been generated from transgenic mice capable of producing human antibodies, as well as from phage libraries of human immunoglobulin; antibodies produced in both manners are of sufficiently low immunogenicity to be applied clinically.