Max-Delbrück-Center for Molecular Medicine, Berlin-Buch, Robert-Rössle-Str. 10, Berlin, Germany.
Cytotherapy. 2011 Jan;13(1):108-13. doi: 10.3109/14653249.2010.515577. Epub 2010 Sep 15.
Humanized mice were generated in order to investigate the anti-tumor efficacy of bispecific antibodies. The engraftment, distribution and differentiation of mononuclear cells (MNC) from cord blood transplanted into the liver of newborn non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice were measured. Using a human-specific polymerase chain reaction (PCR), human cells were found to be present in the liver for a time range from 5 min to 5 days. After long-term engraftment of 42 days, the highest level of human cells was measured in mouse thymus, with lower levels in spleen and bone marrow. Engrafted human cells in mouse organs showed T-cell differentiation only, as measured by CD3, CD4 and CD8 expression. The MNC transplanted intrahepatically into newborn mice were tested for T-cell mediated anti-tumor activity in vivo against subcutaneously transplanted human SW480 colon carcinoma in NOD/SCID mice. A delay of SW480 tumor growth in mice in the presence of a bispecific epithelial cell-adhesion molecule (EpCAM)/CD3 antibody was found to be associated with the presence of immunoreactive human CD3 cells within the SW480 tumor. Our data provide evidence that the intrahepatic transplantation of cord blood stem cells into newborn mice represents a valuable model for establishing functionally active human T cells with anti-tumor activity.
为了研究双特异性抗体的抗肿瘤疗效，生成了人源化小鼠。测量了从脐带血移植到新生非肥胖型糖尿病/严重联合免疫缺陷（NOD/SCID）小鼠肝脏中的单核细胞（MNC）的植入、分布和分化。使用人特异性聚合酶链反应（PCR），发现人细胞在肝脏中存在的时间范围从 5 分钟到 5 天。在 42 天的长期植入后，在鼠胸腺中测量到最高水平的人细胞，在脾和骨髓中的水平较低。在鼠器官中植入的人细胞仅表现出 T 细胞分化，如 CD3、CD4 和 CD8 表达所测量的。将 MNC 经肝内移植到新生小鼠中，在 NOD/SCID 小鼠中对皮下移植的人 SW480 结肠癌细胞进行体内 T 细胞介导的抗肿瘤活性测试。发现存在双特异性上皮细胞黏附分子（EpCAM）/CD3 抗体时，SW480 肿瘤的生长延迟与 SW480 肿瘤内存在免疫反应性人 CD3 细胞有关。我们的数据提供了证据，即脐带血干细胞经肝内移植到新生小鼠中代表了建立具有抗肿瘤活性的功能活跃的人 T 细胞的有价值模型。
