Abstract

Targeting Cancer with BiTE® Antibody Constructs

Roman Kischel, Principal Scientist, Amgen Research

BiTE® antibody constructs are recombinant bispecific antibodies that efficiently recruit host T-cells for redirected killing of cancer cells expressing a selected target antigen. The mode of action of these constructs has been studied extensively. For example the strict dependence of BiTE® antibody construct mediated T-cell activation on the presence of target antigen expressing cells has been shown. Blinatumomab, a CD19/CD3 specific BiTE® antibody construct, has demonstrated substantial clinical activity in B-cell acute lymphoblastic leukemia (ALL). The U.S. Food and Drug Administration (FDA) has granted accelerated approval for blinatumomab for the treatment of adult and pediatric patients with Philadelphia chromosome-negative relapsed or refractory B-cell precursor ALL. Long-term follow-up for a phase 2 study of blinatumomab in patients with minimal residual disease in B-lineage ALL is available. AMG 330, a CD33/CD3 specific BiTE® antibody construct has recently entered a first-in-human trial in patients with relapsed/refractory acute myeloid leukemia. Expression of CD33 has been analyzed in a large number of samples from patients with AML and more than 99% of samples showed CD33 expression. Data from ex-vivo studies using a long-term culture system for AML cells with samples from 38 AML patients suggests substantial antileukemic activity of AMG 330.