title: Eradication of tumor colonization and invasion by a B cell-specific immunotoxin in a murine model for human primary intraocular lymphoma.
abstract: 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.
authors.affiliation: Laboratory of Immunology, National Eye Institute and Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Zhuqing
authors.initials: Z
authors.lastname: Li
authors.forename: Sankaranarayana P
authors.initials: SP
authors.lastname: Mahesh
authors.forename: De Fen
authors.initials: DF
authors.lastname: Shen
authors.forename: Baoying
authors.initials: B
authors.lastname: Liu
authors.forename: Willie O
authors.initials: WO
authors.lastname: Siu
authors.forename: Frank S
authors.initials: FS
authors.lastname: Hwang
authors.forename: Qing-Chen
authors.initials: QC
authors.lastname: Wang
authors.forename: Chi-Chao
authors.initials: CC
authors.lastname: Chan
authors.forename: Ira
authors.initials: I
authors.lastname: Pastan
authors.forename: Robert B
authors.initials: RB
authors.lastname: Nussenblatt
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005134:Eye Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D019718:Receptors, CXCR4 / Q000032:analysis; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine / Q000032:analysis; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000032:analysis
chemical_list: C497867:CD22 protein, human; C095085:CXCR5 protein, human; D000922:Immunotoxins; D019718:Receptors, CXCR4; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D051918:Sialic Acid Binding Ig-like Lectin 2