Abstract 2578: Efficacy of anti-CD22 antibody drug-conjugates in Ramos and Raji tumor xenograft models

Abstract

Abstract CD22 is a well-validated target for immunotherapy on B cell tumors. CD22 is a B lymphoid lineage-specific differentiation antigen, and its cell surface expression coincides with IgD expression in human. CD22 expression is upregulated on mature B cells, and is lost upon terminal differentiation to plasma cells. CD22 is also highly expressed on B cell tumors including non-Hodgkin's lymphoma (NHL) and acute lymphocytic leukemia (ALL). Antibodies to CD22 rapidly internalize, making it an ideal target for an antibody drug conjugate (ADC) therapeutic approach. Human antibodies to CD22 have been generated. The antibodies bind B cells with high affinity and are rapidly internalized upon binding. Anti-CD22 conjugates linked to highly potent synthetic DNA minor-groove binding alkylating (MGBA) agents have been prepared and tested in vivo for the treatment of established Ramos and Raji subcutaneous tumor xenografts. Anti-tumor efficacy of the anti-CD22 conjugate was highly specific in comparison with the isotype control conjugate. The anti-CD22 conjugate at a single dose of 0.3 µmole/kg resulted in regression of established subcutaneous tumors with less than 5% body weight loss and no clinical signs of toxicity. The anti-CD22 conjugate at a single dose of 0.1 µmole/kg was more efficacious than Rituximab treatment on Ramos tumors. The anti-CD22 conjugate also had better tumor growth inhibition than an anti-CD19 conjugate. In summary, anti-CD22-ADCs have been prepared which show superior in vivo efficacy to Rituximab and to anti-CD19-ADCs. 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 2578.