GA-101, a third-generation, humanized and glyco-engineered anti-CD20 mAb for the treatment of B-cell lymphoid malignancies.

Abstract

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.

• Authors: Tadeusz Robak
• Journal: Current opinion in investigational drugs (London, England : 2000) (Curr Opin Investig Drugs) Vol. 10 Issue 6 Pg. 588-96 (Jun 2009) ISSN: 2040-3429 [Electronic] England
• PMID: 19513948 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antigens, CD20
• Antineoplastic Agents
• obinutuzumab

Topics

• Animals
• Antibodies, Monoclonal (immunology, pharmacology, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Antigens, CD20 (immunology)
• Antineoplastic Agents (immunology, pharmacology, therapeutic use)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Clinical Trials, Phase I as Topic
• Clinical Trials, Phase II as Topic
• Drug Evaluation, Preclinical
• Glycosylation
• Humans
• Leukemia, B-Cell (drug therapy, immunology)
• Lymphoma, B-Cell (drug therapy, immunology)
• Mice
• Patents as Topic
• Treatment Outcome
• Xenograft Model Antitumor Assays