title: Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity.
abstract: CD20 is an important target for the treatment of B-cell malignancies, including non-Hodgkin lymphoma as well as autoimmune disorders. B-cell depletion therapy using monoclonal antibodies against CD20, such as rituximab, has revolutionized the treatment of these disorders, greatly improving overall survival in patients. Here, we report the development of GA101 as the first Fc-engineered, type II humanized IgG1 antibody against CD20. Relative to rituximab, GA101 has increased direct and immune effector cell-mediated cytotoxicity and exhibits superior activity in cellular assays and whole blood B-cell depletion assays. In human lymphoma xenograft models, GA101 exhibits superior antitumor activity, resulting in the induction of complete tumor remission and increased overall survival. In nonhuman primates, GA101 demonstrates superior B cell-depleting activity in lymphoid tissue, including in lymph nodes and spleen. Taken together, these results provide compelling evidence for the development of GA101 as a promising new therapy for the treatment of B-cell disorders.
authors.affiliation: GlycArt Biotechnology AG, Schlieren, Switzerland.
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Mössner
authors.forename: Peter
authors.initials: P
authors.lastname: Brünker
authors.forename: Samuel
authors.initials: S
authors.lastname: Moser
authors.forename: Ursula
authors.initials: U
authors.lastname: Püntener
authors.forename: Carla
authors.initials: C
authors.lastname: Schmidt
authors.forename: Sylvia
authors.initials: S
authors.lastname: Herter
authors.forename: Roger
authors.initials: R
authors.lastname: Grau
authors.forename: Christian
authors.initials: C
authors.lastname: Gerdes
authors.forename: Adam
authors.initials: A
authors.lastname: Nopora
authors.forename: Erwin
authors.initials: E
authors.lastname: van Puijenbroek
authors.forename: Claudia
authors.initials: C
authors.lastname: Ferrara
authors.forename: Peter
authors.initials: P
authors.lastname: Sondermann
authors.forename: Christiane
authors.initials: C
authors.lastname: Jäger
authors.forename: Pamela
authors.initials: P
authors.lastname: Strein
authors.forename: Georg
authors.initials: G
authors.lastname: Fertig
authors.forename: Thomas
authors.initials: T
authors.lastname: Friess
authors.forename: Christine
authors.initials: C
authors.lastname: Schüll
authors.forename: Sabine
authors.initials: S
authors.lastname: Bauer
authors.forename: Joseph
authors.initials: J
authors.lastname: Dal Porto
authors.forename: Christopher
authors.initials: C
authors.lastname: Del Nagro
authors.forename: Karim
authors.initials: K
authors.lastname: Dabbagh
authors.forename: Martin J S
authors.initials: MJ
authors.lastname: Dyer
authors.forename: Sibrand
authors.initials: S
authors.lastname: Poppema
authors.forename: Christian
authors.initials: C
authors.lastname: Klein
authors.forename: Pablo
authors.initials: P
authors.lastname: Umaña
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics* / Q000276:immunology / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000920:Antibody-Dependent Cell Cytotoxicity; D018951:Antigens, CD20 / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007141:Immunoglobulin Fc Fragments / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D066298:In Vitro Techniques; D008212:Lymphocyte Depletion / Q000379:methods; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000628:therapy; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000628:therapy; D008252:Macaca fascicularis; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D015202:Protein Engineering; D017452:Receptors, IgG / Q000276:immunology; D000069283:Rituximab; D014183:Transplantation, Heterologous
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D007141:Immunoglobulin Fc Fragments; D007135:Immunoglobulin Variable Region; D017452:Receptors, IgG; D000069283:Rituximab; C543332:obinutuzumab