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E. Bohere, L. Nouvel, G. Besombes, M. Labalette, J.-P. Dessaint, P. Labalette; Synergistic Effect of Serum in Immunotherapy With Rituximab in Local Injection in a Immunocompetent Mouse Model of Primary Intraocular Lymphoma. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3506.
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Primary intraocular lymphomas (PIOL) are aggressive tumors with poor prognosis despite usual treatments. Chimeric anti-CD20 monoclonal antibody (rituximab) greatly improves survival of diffuse large B-cell non-Hodgkin lymphomas, but is not effective on PIOL partly because the blood retina barriers limit antibodies crossing. Moreover, low rate of complement proteins in eye prevents the complement dependent cytotoxicity, one of the mechanisms of action most efficient rituximab.
Human CD20-transfected murine B-lymphoma cells (38C13CD20+) were inoculated in the eye of immunocompetent syngeneic mice. At day 2, 4 and 6 post-inoculation, mice were injected intravitreally with rituximab and serum or rituximab alone. In order to better assess the effects of these therapies, periodic photographs of fund eyes by Topical Endoscopy Fundus Imaging (TEFI) were associated with the daily monitoring of the development of exophthalmos.
In the eye, intravitreal injections of serum alone are well tolerated and the association of rituximab with serum decreased exophthalmia incidence: 0/14 (100%) mice injected with both rituximab and serum developed an exophthalmia, versus 8/14 (58%) with rituximab alone. This optical system allows not only to verify the tumor development but also taken to monitor the development of lymphoma in treatment and to evaluate the effects of disease or treatment.
Rituximab and serum have a synergistic effect. Intravitreal injections of serum alone are well tolerated and association of rituximab and serum are effective on eye involvement in decreasing PIOL occurrence. These results encourage designing human clinical trials including local injections of rituximab with autologous serum, used as complement provider. Moreover the TEFI provides quality retinal imaging in mice. This noninvasive approach helps to better understand the pathophysiology of certain diseases retino-vitreous through mouse models.
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