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cDNA 表达诱导的全身性白细胞介素-12 的安全性作为癌症治疗。

Safety levels of systemic IL-12 induced by cDNA expression as a cancer therapeutic.

机构信息

Inmunología, CIBICI-CONICET, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, 5000, Argentina.

Cancer & Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702-1201 USA.

出版信息

Immunotherapy. 2022 Feb;14(2):115-133. doi: 10.2217/imt-2021-0080. Epub 2021 Nov 16.

Abstract

The aim of this work is to utilize a gene expression procedure to safely express systemic IL-12 and evaluate its effects in mouse tumor models Secondary lymphoid organs and tumors from EL4 and B16 tumor-bearing mice were analyzed by supervised and unsupervised methods. IL-12 cDNA induced systemic IL-12 protein levels lower than the tolerated dose in patients. Control of tumor growth was observed in subcutaneous B16 and EL4 tumors. Systemic IL-12 expression induced a higher frequency of both total tumor-infiltrated CD45 cells and proliferative IFN-γCD8 T cells along with a lower frequency of CD4FOXP3 and CD11bGr-1 cells. This approach characterizes the systemic effects of IL-12, helping to improve treatment of metastases or solid tumors.

摘要

这项工作的目的是利用基因表达程序安全表达系统性 IL-12,并在小鼠肿瘤模型中评估其效果。通过有监督和无监督的方法分析了来自 EL4 和 B16 荷瘤小鼠的次级淋巴器官和肿瘤。IL-12 cDNA 诱导的系统性 IL-12 蛋白水平低于患者可耐受的剂量。在皮下 B16 和 EL4 肿瘤中观察到肿瘤生长的控制。系统性 IL-12 表达诱导了更高频率的总肿瘤浸润性 CD45 细胞和增殖性 IFN-γCD8 T 细胞,同时 CD4FOXP3 和 CD11bGr-1 细胞的频率较低。这种方法描述了 IL-12 的全身效应,有助于改善转移或实体瘤的治疗。

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