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Eradication of Tumor Colonization and Invasion by a B Cell–Specific Immunotoxin in a Murine Model for Human Primary Intraocular Lymphoma

¹ Laboratory of Immunology, National Eye Institute and ² Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland

Requests for reprints: Robert B. Nussenblatt, Laboratory of Immunology, National Eye Institute, NIH, Building 10, Room 10N112, 9000 Rockville Pike, Bethesda, MD 20892. Phone: 301-496-3123; Fax: 301-480-1122; E-mail: DrBob{at}nei.nih.gov.

Human primary intraocular lymphoma (PIOL) is predominantly a B cell–originated malignant disease with no appropriate animal models and effective therapies available. This study aimed to establish a mouse model to closely mimic human B-cell PIOL and to test the therapeutic potential of a recently developed immunotoxin targeting human B-cell lymphomas. Human B-cell lymphoma cells were intravitreally injected into severe combined immunodeficient mice. The resemblance of this tumor model to human PIOL was examined by fundoscopy, histopathology, immunohistochemistry, and evaluated for molecular markers. The therapeutic effectiveness of immunotoxin HA22 was tested by injecting the drug intravitreally. Results showed that the murine model resembles human PIOL closely. Pathologic examination revealed that the tumor cells initially colonized on the retinal surface, followed by infiltrating through the retinal layers, expanding preferentially in the subretinal space, and eventually penetrating through the retinal pigment epithelium into the choroid. Several putative molecular markers for human PIOL were expressed in vivo in this model. Tumor metastasis into the central nervous system was also observed. A single intravitreal injection of immunotoxin HA22 after the establishment of the PIOL resulted in complete regression of the tumor. This is the first report of a murine model that closely mimics human B-cell PIOL. This model may be a valuable tool in understanding the molecular pathogenesis of human PIOL and for the evaluation of new therapeutic approaches. The results of B cell–specific immunotoxin therapy may have clinical implications in treating human PIOL. (Cancer Res 2006; 66(21): 10586-93)

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