In antibody research, the use of mouse models is a key component in several discovery and production processes. For instance, when developing murine monoclonal antibodies, spleen cells of an antigen-exposed mouse are fused to human or mouse myeloma cells, which create the hybridomas needed to produce the desired single antibody clones.
The HAMA response occurs when the human immune system produces antibodies against mouse immunoglobulins or other mouse-derived proteins. When mice are used in research, human subjects (such as patients in clinical trials or individuals exposed to mouse-derived reagents) may develop HAMA due to their exposure to mouse antigens, interfering with therapeutic efficacy. This immune response can occur even after a single exposure and can persist for an extended period, with responses ranging from a mild rash to a life-threatening kidney failure.
To minimize the effect of HAMA on scientific research, researchers can employ several strategies:
Humanized Antibodies: Using humanized or fully human antibodies in research and clinical applications can mitigate the risk of HAMA response. These antibodies are designed to have minimal or no mouse-derived components, reducing the chances of immunogenicity in human subjects.
HAMA Testing and Monitoring: Determining baseline HAMA levels prior to initiation of therapy with murine-derived proteins can help to adjust dosages, interpret results accurately, and tailor treatment approaches accordingly.
Quality Control Measures: Implementing stringent quality control measures during the production and validation of mouse-derived proteins can help minimize potential HAMA-related issues.
Selection of Alternative Animal Models: Researchers can explore alternative animal models that are less likely to trigger the HAMA response. For instance, the use of in vitro techniques such as the production of recombinant monoclonal antibodies would prevent any issues.
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