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Chapter: Pharmaceutical Biotechnology: Fundamentals and Applications - Monoclonal Antibodies in Solid Organ Transplantation

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Monoclonal Antibodies Administered Pre-Transplant

Immunologic barriers to solid organ transplantation are common. Improved management of end-stage organ disease has increased the number of potential organ recipients and produced a significant shortage of organs available for transplant in comparison to the growing demand.

Monoclonal Antibodies Administered Pre-Transplant

 

Immunologic barriers to solid organ transplantation are common. Improved management of end-stage organ disease has increased the number of potential organ recipients and produced a significant shortage of organs available for transplant in comparison to the growing demand. Therefore, clinicians have sought to transplant across previously contraindicated immunologic barriers. In addition, more patients are surviving through their first transplant and are now waiting for a subsequent transplant. Monoclonal antibodies are now being employed prior to trans-plant to desensitize the recipient’s immune system. Desensitization is a strategy where immunosuppres-sion is administered prior to transplant to prevent hyperacute or early rejection in patients who are known to have circulating antibodies against other


human antigens. This strategy is generally reserved for patients who are “highly sensitized” during their evaluation for transplant. Specifically, as a patient develops end-stage organ disease, their medical and immunologic profiles are characterized. Blood sam-ples from these potential recipients are screened for the presence of antibodies against the major histo-compatibility complexes (MHC) on the surface of other human cells, specifically human leukocyte antigens (HLA). Potential recipients who have re-ceived blood products, previous organ transplants, or have a history of pregnancy are at higher risk for the development of antibodies against HLA. In addition, all humans have pre-formed IgG and IgM antibodies against the major blood group antigens (A, B, AB, and A1) (Reid, 2005). These antibodies will recognize donor tissue and quickly destroy (hyperacute rejec-tion) the implanted organ if the tissue contains previously recognized HLA within minutes to hours following transplant. Therefore, it is necessary to evaluate the presence of pre-formed circulating antibodies against HLA in the potential organ recipients. Some centers will implement desensitiza-tion which incorporates monoclonal antibodies prior to transplant to diminish the production of antibodies against a new organ, allowing for transplant across this immunologic barrier.


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