Human anti-mouse 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 per cent of patients. Human anti-mouse 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 an 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 monoclonal administered. In practice, therefore, therapeutic efficacy of murine monoclonals is limited to the first and, at most, the second dose administered. 

The problem is the neutralizing or allergic reactions caused by the production of human anti-mouse antibodies because the body treats the MAbs as foreign (refer to Section 4.3.4). The humanization of antibodies, through chimeric to humanized and full human types, helps to address this problem. 

The advent of recombinant DNA technology led to the development of antibodies and fragments that are tailored for optimal behaviour in vivo [7,8]. Humanized and chimeric antibodies can be constructed to circumvent the human anti-mouse antibody response elicited by mouse antibody treatment of patients, which severely hampers the application of these powerful molecules. The treatment of rheumatoid arthritis patients with doses of as high as 10 mg kg cA2 chimeric antibody specific for TNFa [9], emphasizes that at present the production and purification methods for these proteins have been optimized to such extent that clinical studies can be considerably intensified. 

Lind P, Lechner P, Hausmann B. 1991. Development of human anti-mouse antibodies (HAMA) after single and repeated diagnostic application of intact murine monoclonal antibodies. Antibody Immunoconjug Radiopharm. 4 811-818. 

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]. 

Larsson, A., and Mellstedt, H. (1992) Chicken antibodies a tool to avoid interference by human anti mouse antibodies in ELISA after in vivo treatment with murine monoclonal antibodies. Hybridoma, 11, 33 39. 

CR Complete remission PR Human anti-mouse antibody. 

CR Complete remission PR Partial remission MR Minor remission SD stable disease HAMA Human anti-mouse antibody HACA Human anti-chimeric antibody. 

Human anti-mouse antibody (HAMA) 7, 1109 Human anti-streptavidin antibody (HASA) 513 Human antithrombin... 

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