Eradication of tumor colonization and invasion by a B cell-specific immunotoxin in a murine model for human primary Intraocular lymphoma
Eradication of tumor colonization and invasion by a B cell-specific immunotoxin in a murine model for human primary Intraocular lymphoma
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DOI：
10.1158/0008-5472.can-06-1981
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发表时间：
2006-11-01
期刊：
影响因子：
11.2
通讯作者：
Nussenblatt, Robert B.
中科院分区：
文献类型：
--
作者：
Li, Zhuqing;Mahesh, Sankaranarayana P.;Nussenblatt, Robert B.
人原发性眼内淋巴瘤（PIOL）主要是一种 B 细胞起源的恶性疾病，目前尚无合适的动物模型和有效的治疗方法。本研究旨在建立一种小鼠模型来密切模仿人类 B 细胞 PIOL，并测试最近开发的针对人类 B 细胞淋巴瘤的免疫毒素的治疗潜力。将人 B 细胞淋巴瘤细胞玻璃体内注射到严重联合免疫缺陷小鼠体内。通过眼底镜检查、组织病理学、免疫组织化学检查该肿瘤模型与人类 PIOL 的相似性，并评估分子标记。通过玻璃体内注射药物来测试免疫毒素HA22的治疗效果。结果表明，海洋模型与人类 PIOL 非常相似。病理检查显示，肿瘤细胞最初定植于视网膜表面，随后浸润视网膜各层，优先在视网膜下腔扩张，最终穿透视网膜色素上皮进入脉络膜。在此模型中体内表达了人类 PIOL 的几种推定分子标记。还观察到肿瘤转移至中枢神经系统。 PIOL建立后，单次玻璃体内注射免疫毒素HA22，导致肿瘤完全消退。这是第一个关于紧密模仿人类 B 细胞 PIOL 的小鼠模型的报告。该模型可能是了解人类 PIOL 分子发病机制和评估新治疗方法的宝贵工具。 B 细胞特异性免疫毒素治疗的结果可能对治疗人类 PIOL 具有临床意义。
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 marine 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.