Anti-CD22 and anti-CD79b antibody-drug conjugates preferentially target proliferating B cells.

ABSTRACT:

Background and purpose

CD22 and CD79b are cell-surface receptors expressed on B-cell-derived malignancies such as non-Hodgkin's lymphoma (NHL). An anti-mitotic agent, monomethyl auristatin E, was conjugated to anti-CD22 and anti-CD79b antibodies to develop target-specific therapies for NHL. The mechanism of action (MOA) and pharmacological and pharmacokinetic (PK) profiles of these antibody-drug conjugates (ADCs) were investigated in cynomolgus monkeys.

Experimental approach

Animals were administered anti-CD22 or anti-CD79b ADCs, respective unconjugated antibodies or vehicle. Pharmacodynamic effects on total and proliferating B cells and serum PK were then assessed. Antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) of the ADCs were e

SUBMITTER: Fuh FK 

PROVIDER: S-EPMC5368047 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature