Zuberek Krystyna, Ling Vincent, Wu Paul, Ma Hak-Ling, Leonard John P, Collins Mary, Dunussi-Joannopoulos Kyriaki
Wyeth Research, 200 Cambridgepark Drive, Cambridge, MA 02140, USA.
Cell Immunol. 2003 Sep;225(1):53-63. doi: 10.1016/j.cellimm.2003.09.002.
Increasing evidence suggests that B7/CD28 interactions are important in clonal expansion and effector function of nai;ve CD4(+) T cells, whereas ICOS/GL50 interactions may optimize the responses of recently activated T(H) cells. In tumor models, it has been shown that engagement of ICOS, like CD28, by its ligands can be effective in enhancing tumor immunity. In this report, we have directly compared the in vivo efficacy of CD28 vs ICOS activation in the MethA fibrosarcoma and B16F1 melanoma tumor models. We studied the efficacy of systemic treatment of tumors with murine B7.2-IgG or GL50-IgG fusion proteins, and the therapeutic potential of B7.1 or GL50 vaccines given during various phases of the antitumor responses. In addition, we compare the efficacy of ICOS-ligand splice variants GL50 and GL50B in promoting tumor immunity. We find that each of these pathways is equally effective in promoting tumor immunity and that the efficacy of both GL50 and B7.1 vaccines is IFN-gamma but not IL-10 dependent. Our results suggest that CD28 or ICOS costimulation-based strategies may be equally efficacious as adjuvants to conventional cancer treatment.
越来越多的证据表明，B7/CD28相互作用在初始CD4(+) T细胞的克隆扩增和效应功能中起重要作用，而ICOS/GL50相互作用可能会优化最近激活的T(H)细胞的反应。在肿瘤模型中，已表明ICOS与其配体的结合，如同CD28一样，在增强肿瘤免疫方面是有效的。在本报告中，我们直接比较了在MethA纤维肉瘤和B16F1黑色素瘤肿瘤模型中CD28与ICOS激活的体内疗效。我们研究了用鼠B7.2-IgG或GL50-IgG融合蛋白全身治疗肿瘤的疗效，以及在抗肿瘤反应的不同阶段给予B7.1或GL50疫苗的治疗潜力。此外，我们比较了ICOS配体剪接变体GL50和GL50B在促进肿瘤免疫方面的疗效。我们发现这些途径中的每一种在促进肿瘤免疫方面同样有效，并且GL50和B7.1疫苗的疗效均依赖于IFN-γ而非IL-10。我们的结果表明，基于CD28或ICOS共刺激的策略作为传统癌症治疗的佐剂可能同样有效。
