Anti-CD59 monoclonal antibody, clone YTH53.1 [R-PE]

Background CD59 deficiency is a congenital mutation disorder in complement pathway which can present with various manifestations. Case presentation Herein, we presented an adolescent 16-years-old girl with recurrent attacks of Guillain-Barre in early childhood and then recurrent attacks of angioedema, paresthesia, and myelitis. Finally, she presented with quadriplegia, malar rash, proteinuria, lymphopenia, and high titer of antinuclear antibody. So, the patient developed systemic lupus erythematosus. Furthermore, we performed whole exome sequencing which revealed homozygote mutations in CD59 for the patient and heterozygote one for her parents. CD flow cytometry showed less than 1 percent expression of CD59 on the surface of the patient's peripheral blood cells confirming the disorder. So, she had CD59 deficiency. The patient's episodes were managed with plasma exchanges, corticosteroids, Cyclophosphamide, and Mycophenolate Mofetil which induced and maintained remission. Conclusion CD59 deficiency can be presented with various clinical features such as neurologic, hematologic, dermatologic, and rheumatologic problems including systemic lupus erythematosus.

Purpose: Mantle cell lymphoma (MCL) is a mature B-cell lymphoma considered to be incurable with current treatments, including first-line rituximab in combination with multiagent chemotherapy and for those eligible, high-dose chemotherapy and stem cell support or rituximab maintenance. On the other hand, achieving a complete remission by high-sensitive flow cytometry is associated with prolonged duration of remission, stressing the need to develop and/or incorporate novel agents into the management of MCL. To this end, we examined the activity of ofatumumab, an anti-CD20 monoclonal antibody with distinct binding and immunologic properties compared to rituximab, in MCL preclinical models. Experimental Design: MCL cells were labeled with Cr-51 before incubation with rituximab or ofatumumab (10 mg/mL) plus human serum or effector cells. Cr-51-release was measured and the percentage of lysis was calculated. Surface CD20, CD55, and CD59 were measured by Imagestream analysis. SCID mice inoculated subcutaneously with Z138 cells were assigned to control versus four doses of ofatumumab or rituximab (10 mg/kg/dose). Results: Ofatumumab exhibited enhanced in vitro complement- dependent cytotoxicity activity compared with rituximab in MCL cell lines, despite a high degree of in vitro resistance to rituximab associated with low CD20 levels and/or high expression of complement inhibitory proteins. Ofatumumab also delayed tumor progression and prolonged survival in a murine model of MCL. Conclusions: Our results demonstrate that ofatumumab is more effective than rituximab in MCL preclinical models, including in the presence of rituximab resistance, and support the clinical investigation of ofatumumab in combination with standard systemic chemotherapy in MCL (NCT01527149). (C) 2015 AACR.