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

Curr Opin Investig Drugs. 2009 Jun;10(6):588-96.

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.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD20 / immunology*
  • Antineoplastic Agents / immunology
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / 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*
  • Leukemia, B-Cell / immunology
  • Lymphoma, B-Cell / drug therapy*
  • Lymphoma, B-Cell / immunology
  • Mice
  • Patents as Topic
  • Treatment Outcome
  • Xenograft Model Antitumor Assays

Substances

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