Department of Immunology, H. Lee Moffitt Cancer Center, MRC 2067, 12902 Magnolia Dr. Tampa, Tampa, FL 33647, USA.
Cancer Immunol Immunother. 2012 Apr;61(4):573-9. doi: 10.1007/s00262-011-1198-9. Epub 2012 Jan 6.
In this study, we tested the effect of intratumoral administration of dendritic cells (DCs) with inducible expression of different cytokines, using the novel Rheoswitch Therapeutic System on the experimental models of renal cell cancer (RENCA) and MethA sarcoma. Intratumoral injection of DCs, engineered to express IL-12, IL-21, or IFN-α, showed potent therapeutic effect against established tumor. This effect was associated with the induction of potent tumor antigen-specific CD8+ T-cell responses, as well as the infiltration of tumors with CD4+ and CD8+ T cells but not with the cytotoxic activity of DCs. Combination of i.t. administration of DCs, producing different cytokines, did not enhance the antitumor effect of therapy with single cytokine. These results indicate that RTS can be a potent tool for conditional topical cytokine delivery, in combination with DC administration. However, combination of different cytokines may not necessarily improve the outcome of treatment.
在这项研究中，我们使用新型 Rheoswitch 治疗系统，测试了在肾细胞癌 (RENCA) 和 MethA 肉瘤的实验模型中，肿瘤内给予可诱导表达不同细胞因子的树突状细胞 (DC) 的效果。肿瘤内注射经工程改造表达 IL-12、IL-21 或 IFN-α 的 DC 对已建立的肿瘤显示出强大的治疗效果。这种效果与诱导强烈的肿瘤抗原特异性 CD8+T 细胞反应以及 CD4+和 CD8+T 细胞浸润肿瘤有关，但与 DC 的细胞毒性活性无关。不同细胞因子的联合 i.t. 给药并未增强单一细胞因子治疗的抗肿瘤作用。这些结果表明，RTS 可以成为与 DC 给药联合使用的条件性局部细胞因子递送的有效工具。然而，不同细胞因子的联合不一定能改善治疗效果。
