Murine mAbs HAMA responses

The therapeutic application of antibodies of non-human origin may cause problems because murine mAbs are recognized by the human immune system as extrinsic substances. In general, the first administration of 100% murine mAbs is well tolerated. However, it can induce the production of specific anti-antibodies by the human body, the so-called human anti-murine antibodies (HAMAs), against the murine mAbs. Repeated administration of 100% murine mAbs may cause an immune response with influenza-like symptoms and even severe states of shock. 

Because most monoclonal antibodies that have been studied for tissue targeting are from mouse or, occasionally, from rat, the problem of antibody production to such foreign proteins always exists. While murine-derived mAbs are well tolerated for acute therapy, their use in chronic therapy is limited, due to severe human anti-mouse antibody response (HAMA) [231]. The HAMA response is elicited due to the foreign nature of the antibody itself. Molecular engineering is being utilized to replace the foreign components of the murine antibody with human antibody sequences to overcome their immunogenicity [232]. 

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. 

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