• Rym Ben Abdelwahed, Sabrina Donnou, Hanane Ouakrim, Lucile Crozet, Jérémie Cosette, Alexandra Jacquet, Isabel Tourais, Bénédicte Fournès, Mélanie Gillard Bocquet, Amine Miloudi, Valérie Touitou, Cécile Daussy, Marie-Christine Naud, Wolf Herman Fridman, Catherine Sautès-Fridman, Rémi Urbain, and Sylvain Fisson.
• INSERM UMRS 951, 1 bis rue de l'Internationale, Evry F-91002, France.
• Invest. Ophthalmol. Vis. Sci. 2013 May 1; 54 (5): 3657-65.

PurposePrimary 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.MethodsThe 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.ResultsSingle 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.ConclusionsThese 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.

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