title: Preclinical study of Ublituximab, a Glycoengineered anti-human CD20 antibody, in murine models of primary cerebral and intraocular B-cell lymphomas.
abstract: OBJECTIVE
  Primary cerebral lymphoma (PCL) and primary intraocular lymphoma (PIOL) belong to the systemic diffuse large B-cell lymphoma family and are characterized by the presence of CD20(+) lymphoma B cells in the brain or the eye. These highly aggressive malignancies have a poor prognosis and no specific therapy. The presence of effector immune cells in the damaged brain and vitreous suggests that treatment with anti-human CD20 (hCD20) monoclonal antibodies might be effective. We developed murine models of PCL and PIOL to assess the intracerebral and intraocular antitumor effect of ublituximab, a promising glycoengineered anti-hCD20 mAb with a high affinity for FcγRIIIa (CD16) receptors.
  
  
  METHODS
  The murine lymphoma B-cell line A20.IIA-GFP-hCD20 (H-2(d)) was injected into the right cerebral striatum or the vitreous of immunocompetent adult BALB/c mice (H-2(d)). Four to 7 days later, ublituximab was injected intracerebrally or intravitreously into the tumor site. Rituximab was the reference compound. Survival was monitored for injected mice; histopathological and flow cytometric analyses were performed to study tumor growth and T-cell infiltration.
  
  
  RESULTS
  Single doses of ublituximab, injected intracerebrally or intravitreously, had a marked antitumor effect, more pronounced than that obtained with the same dose of rituximab in these conditions. The reduction in tumor cells was correlated with an increased proportion of CD8(+) T cells. This efficacy was observed only against lymphoma B cells expressing hCD20.
  
  
  CONCLUSIONS
  These in vivo results confirm the potential of the glycoengineered anti-hCD20 mAb ublituximab as an innovative therapeutic approach to treat primary central nervous system lymphoma and other B-cell lymphomas.
authors.affiliation: INSERM UMRS 951, 1 bis rue de l'Internationale, Evry F-91002, France.
authors.forename: Rym
authors.initials: R
authors.lastname: Ben Abdelwahed
authors.forename: Sabrina
authors.initials: S
authors.lastname: Donnou
authors.forename: Hanane
authors.initials: H
authors.lastname: Ouakrim
authors.forename: Lucile
authors.initials: L
authors.lastname: Crozet
authors.forename: Jérémie
authors.initials: J
authors.lastname: Cosette
authors.forename: Alexandra
authors.initials: A
authors.lastname: Jacquet
authors.forename: Isabel
authors.initials: I
authors.lastname: Tourais
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Fournès
authors.forename: Mélanie
authors.initials: M
authors.lastname: Gillard Bocquet
authors.forename: Amine
authors.initials: A
authors.lastname: Miloudi
authors.forename: Valérie
authors.initials: V
authors.lastname: Touitou
authors.forename: Cécile
authors.initials: C
authors.lastname: Daussy
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Naud
authors.forename: Wolf Herman
authors.initials: WH
authors.lastname: Fridman
authors.forename: Catherine
authors.initials: C
authors.lastname: Sautès-Fridman
authors.forename: Rémi
authors.initials: R
authors.lastname: Urbain
authors.forename: Sylvain
authors.initials: S
authors.lastname: Fisson
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology; D018951:Antigens, CD20 / Q000276:immunology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000276:immunology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005134:Eye Neoplasms / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D015202:Protein Engineering; D000069283:Rituximab; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D000069283:Rituximab
keywords: glycoengineered monoclonal antibody; human CD20; primary intracerebral B cell lymphoma (PCL); primary intraocular B cell lymphoma (PIOL); primary vitreoretinal lymphoma (PVRL); ublituximab