Human antimouse antibody

Antibody immunogenicity remains one of the inherent therapeutic limitations associated with administration of murine monoclonals to human subjects. In most instances, a single injection of the murine monoclonal will elicit an immune response in 50-80% of patients. Human antimouse antibodies (HAMA) will generally be detected within 14 days of antibody administration. Repeated administration of the monoclonal (usually required if the monoclonal is used for therapeutic purposes) will increase the HAMA response significantly. It will also induce a HAMA response in the majority of individuals who display no such response after the initial injection. The HAMA response will effectively and immediately destroy subsequent doses of... 

DTH Delayed-type hypersensitivity FKBP FK-binding protein HAMA Human antimouse antibody HLA Human leukocyte antigen IFN Interferon... 

The use of specific and nonspecific antisera in human medicine is well established and dates back to 1891 when Emil von Behring developed the first diphtheria antitoxin, but their use carries associated risks such as fluid overload and transmission of disease. The potential for MABs as therapeutic agents was quickly recognized and the first MAB was approved for therapeutic use in 1986 (Ortho Biotech s OKT3, a mouse MAB to CD3, for the reversal of transplant rejection). It became clear early on that the presence of, or appearance of, human antimouse antibodies (HAMA) in the patient, which neutralized subsequent treatments, often limited the efficacy of mouse MABs. More recently, chimeric, deimmunized, or fully human MABs have been developed. 

One of the major obstacles to successful MAT was the limitation of the applicability of murine (or other xenogeneic) mAbs. Their biologic activity in the human environment is limited, since the host s immune response to these antibodies, namely production of human antimouse antibodies (HAMAs), is not only potentially associated with undesirable and sometimes life-threatening clinical side effects, but also with neutralization or enhanced elimination of the therapeutic mAb. This could be partly prevented by concomitant immunosuppression, including the use of immunosuppressive mAbs as in the case of organ transplantation. 

Compared with the therapeutic use of human monoclonal antibodies, the use of rodent (mouse or rat) monoclonal antibodies in vivo is disadvantageous because the xenogeneic antibody can induce immune responses that will mitigate the effectiveness of the antibody and/or cause adverse reactions in the recipient. Thus, the authors of one report concluded that antimouse immunoglobulin responses in human patients have limited the usefulness of murine monoclonal antibodies in more than half of those treated (12). The formation of human antimouse antibodies has been described both when murine monoclonal antibodies are used as a diagnostic tool in vivo and when they are used therapeutically (13-16). 

Norman DJ, Chatenoud L, Cohen D, Goldman M, Shield CF 3rd. Consensus statement regarding OKT3-induced cytokine-release syndrome and human antimouse antibodies. Transplant Proc 1993 25(2 Suppl l) 89-92. 

Preincubation of the study samples with animal antibodies or serum has been reported to substantially decrease positive interference due to heterophilic antibodies by preventing, for example, heterophilic human antimouse antibodies present in the study samples from cross-linking the reagent antibodies [37,39]. These types of reagents are produced commercially for such purposes. 

Patients with known allergies or hypersensitivity to mouse proteins, human antimouse antibodies (HAMA) titers should be determined before administration of Tc-CEA-Scan. 

FIGURE 92.2 Schematic diagram of a sandwich immunoassay for cardiac troponin, (a) True positive result in the presence of the antigen, (b) False-positive result in the presence of an interfering antibody. HAMA = human antimouse antibody. 

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