Abstract 2452: Efficacy and toxicity of an anti-CD19 antibody drug conjugate

CD19 is an attractive target for immunotherapy. The expression of CD19 is restricted to B cells and follicular dendritic cells. In B cells, expression is initiated at the point of B lineage commitment and continues through the pre B and mature B cell differentiation. Expression is lost during the terminal differentiation of B cells to plasma cells. CD19 expression continues in B-lineage cells that have undergone neoplastic transformation, making it a useful marker in diagnosis and treatment of B cell derived lymphomas and leukemias, including non-Hodgkin9s lymphoma (NHL), acute lymphocytic leukemia (ALL) and chronic lymphocytic leukemia (CLL). We have generated a fully human antibody to CD19 (MDX-1435) in transgenic mice for high binding affinity as well as the ability to rapidly internalize for drug delivery. The antibody was conjugated to a potent DNA alkylating agent related to Duocarmycin (MED-2460). This ADC (MDX-1206) shows anti-tumor activity in established Raji, Daudi and Ramos subcutaneous xenograft models at doses as low as 0.1 μmole/kg with no associated weight loss, or other overt toxicity. Efficacy was substantially superior to that of MDX-1435 and non-specific control antibody conjugates. In addition, MDX-1435 binds to cynomologus monkey CD19 with similar affinity and tissue distribution as in humans. The intravenous administration of two doses at 0.4 μmole/kg was well tolerated in cynomologus monkeys and did not result in overt clinical or histological signs of toxicity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2452.