Glycart Biotechnology AG, Genentech Inc, F Hoffmann-La Roche Ltd, Biogen Idec Inc and Chugai
Pharmaceutical Co Ltd are developing
GA-101, a third-generation, humanized and glyco-engineered anti-CD20
IgG1 mAb, for the potential treatment of B-cell
malignancies. Compared with classic type I CD20
antibodies (eg,
rituximab),
GA-101 binds with high affinity to the CD20 type II
epitope, resulting in the induction of antibody-dependent cytotoxicity that is 5- to 100-fold greater than observed upon treatment with
rituximab.
GA-101 also exhibits superior direct cell killing properties than
rituximab. In preclinical studies,
GA-101 was significantly more potent and effective in depleting B-cells than
rituximab, and induced dose-dependent antitumor activity, complete
tumor regression and improved long-term survival in xenograft mouse models of B-cell
malignancy. In a phase I/II clinical trial,
GA-101 had a similar safety profile to
rituximab, and exhibited promising efficacy in patients with relapsed/refractory CD20-positive lymphoid
malignancies. At the time of publication, phase I/II trials for
GA-101 were ongoing in B-cell
malignancies. Based on preclinical and preliminary clinical data,
GA-101 appears to be a promising therapeutic agent for CD20-positive B-cell lymphoid malignances, including non-Hodgkin
lymphomas and
chronic lymphocytic leukemia.