Faculty of Biotechnology and Food Engineering, Technion-Israel Institute of Technology, Haifa, Israel.
Cancer Sci. 2012 Jan;103(1):116-24. doi: 10.1111/j.1349-7006.2011.02124.x. Epub 2011 Nov 27.
Fas ligand (CD95L/APO-1) is considered as a potent anti-tumor agent due to its mediated cell death properties. We have designed a polymeric microencapsulation system, which encapsulates soluble FasL secreting cells. The encapsulated cells continuously release soluble FasL (sFasL) at the tumor site, while the device protects the encapsulated cells from the host immune system. The potential and efficacy of this system are demonstrated in vitro and in vivo for tumor inhibition. Polymeric microcapsules composed of Alginate Poly-l-lysine were optimized to encapsulate L5 secreting sFasL cells. The expression and anti-tumor activities of the sFasL were confirmed in vitro and tumor inhibition was studied in vivo in SCID mice bearing subcutaneous lymphoma tumors. In vitro, sFasL secreted by the encapsulated L5-sFasL cells was biologically active, inhibited proliferation and induced apoptotic cell death in Fas sensitive tumor cells. Mice injected with encapsulated L5-sFasL cells on the day of tumor injection or 10 days after tumor injection showed significant reduction in tumor volume, of 87% and 95%, respectively. Our findings show that encapsulated cells expressing sFasL can be used as a local device and efficiently suppress malignant Fas sensitive tumors with no side effects.
Fas 配体（CD95L/APO-1）因其介导的细胞死亡特性而被认为是一种有效的抗肿瘤药物。我们设计了一种聚合物微囊化系统，该系统可以包裹分泌可溶性 FasL 的细胞。包封的细胞在肿瘤部位持续释放可溶性 FasL（sFasL），同时该装置保护包封的细胞免受宿主免疫系统的攻击。该系统的潜力和疗效已在体外和体内肿瘤抑制方面得到证实。由藻酸盐聚赖氨酸组成的聚合物微胶囊被优化以包裹分泌 sFasL 的 L5 细胞。体外实验证实了 sFasL 的表达和抗肿瘤活性，并在携带皮下淋巴瘤肿瘤的 SCID 小鼠体内研究了肿瘤抑制作用。体外实验表明，包封的 L5-sFasL 细胞分泌的 sFasL 具有生物活性，可抑制 Fas 敏感肿瘤细胞的增殖并诱导其凋亡性细胞死亡。在肿瘤注射当天或肿瘤注射后 10 天向小鼠注射包封的 L5-sFasL 细胞，肿瘤体积分别显著减少了 87%和 95%。我们的研究结果表明，表达 sFasL 的包封细胞可用作局部装置，有效地抑制恶性 Fas 敏感肿瘤，且无副作用。
