Nagarajan Shanmugam, Selvaraj Periasamy
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, 1639 Pierce Drive, Atlanta, GA 30322, USA.
Cancer Res. 2002 May 15;62(10):2869-74.
Systemic or local administration of cytokine has been used as a mode to enhance the antitumor immune response induced by many cancer vaccines. We have investigated whether the expression of cytokines on the tumor cell surface as a glycolipid (GPI)-anchored form will be effective in inducing antitumor immune response using a GPI-anchored interleukin (IL)-12 (GPI-IL-12) as a model. GPI-IL-12-induced the proliferation of concanavalin A-activated T cells and induced IFN-gamma secretion by activated and allogeneic T cells, indicating that the membrane-expressed IL-12 can stimulate T cells. GPI-IL-12 expressed on the tumor cell surface prevented tumor growth in mice in a highly tumorigenic murine mastocytoma model. These results suggest that the cell surface-expressed GPI-IL-12 can be effective in inducing antitumor immune response, and GPI-anchored cytokines expressed on the tumor cell surface may be a novel approach to deliver cytokines at the immunization site during vaccination against cancer. Furthermore, purified GPI-anchored cytokines can be used to quickly modify tumor membranes by the protein transfer method to express the desired cytokines for vaccine development.
细胞因子的全身或局部给药已被用作增强多种癌症疫苗诱导的抗肿瘤免疫反应的一种方式。我们以糖基磷脂酰肌醇（GPI）锚定形式的白细胞介素（IL）-12（GPI-IL-12）为模型，研究了肿瘤细胞表面细胞因子的表达是否能有效诱导抗肿瘤免疫反应。GPI-IL-12诱导了伴刀豆球蛋白A激活的T细胞增殖，并诱导活化的和同种异体T细胞分泌γ干扰素，这表明膜表达的IL-12可以刺激T细胞。在高致瘤性小鼠肥大细胞瘤模型中，肿瘤细胞表面表达的GPI-IL-12可抑制小鼠肿瘤生长。这些结果表明，细胞表面表达的GPI-IL-12可有效诱导抗肿瘤免疫反应，肿瘤细胞表面表达的GPI锚定细胞因子可能是在癌症疫苗接种期间在免疫部位递送细胞因子的一种新方法。此外，纯化的GPI锚定细胞因子可通过蛋白质转移方法快速修饰肿瘤膜，以表达用于疫苗开发的所需细胞因子。
