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C. Karkoutly, J.-F. Mineo, A. Scheffer, L. Nouvel, J. Trauet, J.-P. Dessaint, M. Labalette, C. Berthou, P. Labalette; Intravitreal and Intracerebral Rituximab Injections in Murine Models of B-Cell Primary Intraocular and Central Nervous System Lymphomas. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5679.
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Primary intraocular lymphoma (PIOL) is a subset of primary central nervous system lymphoma (PCNSL) with a poor prognosis despite recent improvements in diagnosis and treatment. The purpose of this study is to evaluate the efficiency of intravitreal and intracerebral anti-CD20 monoclonal antibody (rituximab) injections in immunocompetent murine models of B-cell PIOL and PCNSL.
Human CD20-transfected murine B-lymphoma cells (38C13CD20+) were inoculated in the vitreous via the pars plana or in the caudate nucleus in immunocompetent syngeneic mice. Native 38C13 cells were used as control for the injections. Then rituximab (or control by PBS) was injected intravitreally on day 1, 3, 5 or intracerebrally on day 1. Animals were examined daily. Animals were sacrified when exophthalmia, neurological disturbance and body weight loss occurred or at the end of the study.
The expression of human CD20 by the 38C13CD20+ cell line and the cytotoxicity of rituximab on the 38C13CD20+ cells was controlled in vitro.28 and 24 mice were implanted in the eye and in the brain respectively. Significantly fewer mice 9/19 (47%) in the rituximab group developed intraocular tumors presenting with exophthalmia than in the PBS group (9/9, 100%). Exophthalmia appeared later (median of 24,8 days) in the 9 mice that developed an ocular tumor despite receiving rituximab than these receiving PBS intravitreal injections (median of 15 days). For the intracerebral injections, the tumor occurrence decreased in frequency: 33% in mice injected with rituximab versus 78% in control mice injected with PBS.
Intravitreal and intracerebral rituximab injections reduced tumor occurrence and growth in each model. Our intraocular and intracerebral models with inoculation of human CD20-transfected murine 38C13 cells in the vitreous or the brain of immunocompetent mice are suitable to evaluate PIOL and PCNSL treatment.
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