Pharmacodynamic effects of administration of maytansine conjugated anti-CD22 monoclonal antibodies to cynomolgus monkeys

3051 Antibody-based B-cell specific therapeutic approaches have revolutionized the treatment of non-Hodgkin's lymphomas (NHL) as well as other hematological malignancies. However, a large variability in clinical response has been observed, and the need to develop effective new treatments remains urgent. A promising approach is the use of antibody-drug conjugates (ADCs), cytotoxic drugs covalently linked to antibodies through specialized chemical linkers for the treatment of NHL. CMC-544, an antibody to a B-cell specific glycoprotein CD22 conjugated to the cytotoxin calicheamicin, has shown clinical activity in patients. In addition, antibodies directed to B-cell targets such as rituximab and epratuzumab are in clinical trials for the treatment of NHL and autoimmune disorders. We have generated10F4v3, an anti-CD22 antibody conjugated to the antimitotic agent maytansine (10F4v3-DM1). DM1 disrupts cellular mitosis through inhibition of tubulin polymerization when internalized into cells. The anti-CD22 DM1 co...