GA-101, a third-generation, humanized and glyco-engineered anti-CD20 mAb for the treatment of B-cell lymphoid malignancies.
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.
Robak
Tadeusz
T
Medical University of Lodz and Copernicus Memorial Hospital, Department of Hematology, 93-510 Lodz, Ciolkowskiego 2, Poland. robaktad@csk.umed.lodz.pl
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018951:Antigens, CD20 / Q000276:immunology*; D000970:Antineoplastic Agents / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004353:Drug Evaluation, Preclinical; D006031:Glycosylation; D006801:Humans; D015448:Leukemia, B-Cell / Q000188:drug therapy* / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D010330:Patents as Topic; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018951:Antigens, CD20; D000970:Antineoplastic Agents; C543332:obinutuzumab