Preclinical study of Ublituximab, a Glycoengineered anti-human CD20 antibody, in murine models of primary cerebral and intraocular B-cell lymphomas

Invest Ophthalmol Vis Sci. 2013 May 1;54(5):3657-65. doi: 10.1167/iovs.12-10316.


Purpose: 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.

Keywords: glycoengineered monoclonal antibody; human CD20; primary intracerebral B cell lymphoma (PCL); primary intraocular B cell lymphoma (PIOL); primary vitreoretinal lymphoma (PVRL); ublituximab.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal, Murine-Derived / pharmacology
  • Antigens, CD20 / immunology*
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Central Nervous System Neoplasms / drug therapy*
  • Central Nervous System Neoplasms / immunology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Eye Neoplasms / drug therapy*
  • Eye Neoplasms / immunology
  • Female
  • Humans
  • Lymphoma, B-Cell / drug therapy*
  • Lymphoma, B-Cell / immunology
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Transplantation
  • Protein Engineering
  • Rituximab
  • Xenograft Model Antitumor Assays


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20
  • Antineoplastic Agents
  • Rituximab