STABLE CLONE PRODUCTION FOR ANTI-EBV MONOCLONAL ANTIBODIES

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Epstein-Barr virus (EBV) is the major cause of post-transplant lymphoproliferative disease (PTLD) and EBV lymphoma in stem cell and organ transplant recipients. Persons who are EBV seronegative before transplant have a 10- to 76-fold higher risk of developing PTLD than EBV seropositive persons. Persons with X-linked lymphoproliferative disease, severe combined immunodeficiency, and certain other immunodeficiencies are at high risk for developing fatal EBV disease, including lymphomas, with primary infection. Thus, infusion of monoclonal antibodies into EBV seronegative immunocompromised persons may reduce the incidence of PTLD or EBV lymphomas. In a mouse transplant model (using humanized mice), the National Institute of Allergy and Infectious Diseases (NIAID) found that giving the mice either of the two monoclonal antibodies (mAbs), EBV mAb A10-V2-LS or EBV mAb B10-LS, protected the animals from EBV viremia and EBV lymphomas. The Division of Cancer Treatment and Diagnosis, NCI in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID) is requesting the generation of stable clones for anti-Epstein-Barr virus (EBV) monoclonal antibodies. Successful production of stable clones resulting from this Task Order will support future manufacturing process development and the cGMP production of two, novel anti-EBV antibodies for evaluation in preclinical and human clinical studies. These antibodies target EBV gH/gL and EBV gp42, and potently neutralize EBV infection, block fusion, and protect humanized mice from death, viremia, EBV tissue infiltration, and lymphoma. Additionally, these antibodies are the most potent gH/gL mAb and gp42 mAb to date and might be used to prevent EBV infection or disease in transplant recipients or in immunocompromised individuals who may not respond well to EBV vaccines.