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L. Nouvel, J.-F. Mineo, C. Karkoutly, A. Scheffer, C.-A. Maurage, J.-P. Dessaint, M. Labalette, P. Labalette; Intravitreal Rituximab and Serum Are Synergistic for Primary Intraocular Lymphoma Treatment in an Immunocompetent Mice Model. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5751.
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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 most efficient rituximab mechanisms of action.
In vitro, human CD20-transfected murine B-lymphoma cells (38C13 CD20+) were incubated with rituximab alone or with serum (providing complement). In vivo, 38C13 CD20+ cells 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, rituximab alone or an irrelevant antibody and serum. Clinical symptoms occurrence of eye involvement were monitored and MRI sequences (T2) were performed when exophthamia appeared. Moreover serum was injected alone without tumor inoculation.
In vitro, rituximab and serum have a synergistic effect for cell death induction. In the eye, intravitreal injections of serum alone are well tolerated and the association of rituximab with serum decreased exophthalmia incidence: 8/14 (58%) mice injected with both rituximab and serum developed an exophthalmia, versus 11/12 (92%) with rituximab alone and 12/12 (100%) in the control group. When exophthamia clinically appeared, MRI evidenced an ocular layer thickening and a retro-ocular isointense tumoral mass.
Rituximab and serum have a synergistic effect both in vitro and in vivo experiments. 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.
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