Liposomal transfection of squamous carcinoma cells of the head and neck with IL-2 and B7 plasmids inducing an autologous immune response in vitro.
Liposomal transfection of squamous carcinoma cells of the head and neck with IL-2 and B7 plasmids inducing an autologous immune response in vitro.
复制标题
用 IL-2 和 B7 质粒脂质体转染头颈鳞状癌细胞，在体外诱导自体免疫反应。
作者：
A. Mayer;M. Andratschke;C. Pauli;Eva Reitberger;Kristina Kolbow;B. Wollenberg
需要制定新的治疗策略来应对头颈鳞状细胞癌（SCCHN）发病率和死亡率不断上升的情况，因为总体生存率仍然很低，而且在过去四十年中取得了微小的治疗进展。一个主要目标可能是通过肿瘤内注射 IL-2 基因来恢复受损的免疫系统，该基因在肿瘤部位永久提供无毒的 IL-2 蛋白浓度，足以激活体内细胞免疫。我们表明，用封装在 DOTMA/Col 中的 IL-2 质粒转染 SCCHN 细胞系，可在体外导致肿瘤细胞自身合成生物活性 IL-2 蛋白长达 30 天。次级细胞因子（IL-6、IL-8、GM-CSF、TNF-α）的转录和免疫调节表面分子（MHC II 类、ICAM1）的表达增强。 IL-2修饰的肿瘤细胞被自体外周血淋巴细胞（PBL）有效裂解。 B7.1基因共转染和/或用外源IL-2预激活PBL可增强免疫反应。我们证明体外脂质体介导的 SCCHN 细胞 IL-2 基因转染是刺激自体免疫反应的有效方法，因此具有临床应用前景。
New treatment strategies need to be developed to face the increasing incidence and mortality of squamous cell carcinoma of the head and neck (SCCHN), as the overall survival rate remains poor, with minor therapeutic progress having been achieved over the past forty years. One major goal could be to restore a damaged immune system by intratumoral injection of IL-2-genes that permanently provide non-toxic IL-2-protein concentrations at the tumor site, sufficient to activate cellular immunity in vivo. We showed that the transfection of SCCHN cell lines with IL-2-plasmids, encapsulated in DOTMA/Col, in vitro resulted in the synthesis of bioactive IL-2-protein for up to 30 days by the tumor cells themselves. The transcription of secondary cytokines (IL-6, IL-8, GM-CSF, TNF-alpha) and the expression of immunomodulatory surface molecules (MHC Class II, ICAM1) were enhanced. The IL-2-modified tumor cells were effectively lysed by autologous peripheral blood lymphocytes (PBLs). The immune response was enhanced by B7.1-gene-cotransfection and/or preactivation of PBLs with exogenous IL-2. We demonstrated that in vitro liposome-mediated IL-2-gene-transfection of SCCHN cells is an effective method to stimulate an autologous immune response and is, therefore, promising for clinical application.
DOI：
10.1083/jcb.131.5.1149
发表时间：
1995-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lin KI;Lee SH;Narayanan R;Baraban JM;Hardwick JM;Ratan RR
通讯作者：
Ratan RR
使用分泌 IL-2 的肿瘤细胞进行疫苗接种可刺激 IL-2 反应性 T 细胞的产生，并防止无反应性的发生。
影响因子：
6.4
作者：
Zier,KS;Salvadori,S;Cronin,KC;Gansbacher,B
通讯作者：
Gansbacher,B
B7.1 对人类癌症的作用：T 细胞的共刺激和增强肿瘤诱导的 T 细胞死亡。
影响因子：
4.3
作者：
Lang,S;Atarashi,Y;Nishioka,Y;Stanson,J;Meidenbauer,N;Whiteside,TL
通讯作者：
Whiteside,TL