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一种靶向 MUC1 的新型治疗性肿瘤疫苗联合 PD-L1 在小鼠中引发特异性抗肿瘤免疫

英文原题:A Novel Therapeutic Tumor Vaccine Targeting MUC1 in Combination with PD-L1 Elicits Specific Anti-Tumor Immunity in Mice.

PubMed 2022/07/08(内容时间) Vaccines (Basel) Q2 · IF 3.5(JCR 2025)

研究概要

我们的研究为提高治疗性疫苗的交叉呈递能力提供了一种新的免疫治疗策略,该策略可能适用于胰腺癌、肺癌以及靶向其他高表达MUC1和PD-L1的实体瘤类型。

中文摘要

树突状细胞(DC)作为专业抗原呈递细胞,在启动和调节体液及细胞免疫中发挥关键作用。负载不同肿瘤相关抗原(TAA)的DC疫苗已广泛用于研究癌症治疗效果。多项临床试验表明,DC作为抗肿瘤疫苗具有安全性,并能激活一定的抗肿瘤免疫应答;然而DC疫苗整体临床疗效仍不理想,需进一步增强。MUC1是一种具有较大潜力的TAA,免疫检查点PD-L1也有望用于肿瘤治疗,两者在多种肿瘤细胞表面高表达。本研究基于近期开发的PD-L1-Vax疫苗方法,制备新型治疗性MUC1-Vax肿瘤疫苗。该含PD-L1的新型MUC1-Vax疫苗在免疫小鼠中提高了持续产生抗PD-L1抗体的水平,并引发更强的保护性细胞毒性T淋巴细胞(CTL)应答。此外,MUC1-Vax疫苗对肿瘤具有显著治疗作用,可显著抑制高表达MUC1和PD-L1的LLC及Panc02肿瘤细胞生长,并延长荷瘤动物的生存。总之,本研究提出一种增强治疗性疫苗交叉呈递能力的新免疫治疗策略,可能适用于胰腺癌、肺癌及其他MUC1和PD-L1高表达的实体瘤。

展开英文摘要原文

Dendritic cells (DCs), as professional antigen-presenting cells (APCs), play a key role in the initiation and regulation of humoral and cellular immunity. DC vaccines loaded with different tumor-associated antigens (TAAs) have been widely used to study their therapeutic effects on cancer. A number of clinical trials have shown that DCs are safe as an antitumor vaccine and can activate certain anti-tumor immune responses; however, the overall clinical efficacy of DC vaccine is not satisfactory, so its efficacy needs to be enhanced. MUC1 is a TAA with great potential, and the immune checkpoint PD-L1 also has great potential for tumor treatment. Both of them are highly expressed on the surface of various tumors. In this study, we generated a novel therapeutic MUC1-Vax tumor vaccine based on the method of PD-L1-Vax vaccine we recently developed; this novel PD-L1-containing MUC1-Vax vaccine demonstrated an elevated persistent anti-PD-L1 antibody production and elicited a much stronger protective cytotoxic T lymphocyte (CTL) response in immunized mice. Furthermore, the MUC1-Vax vaccine exhibited a significant therapeutic anti-tumor effect, which significantly inhibited tumor growth by expressing a high MUC1 + and PD-L1 + level of LLC and Panc02 tumor cells, and prolonged the survival of cancer-bearing animals. Taken together, our study provides a new immunotherapy strategy for improving the cross-presentation ability of therapeutic vaccine, which may be applicable to pancreatic cancer, lung cancer and for targeting other types of solid tumors that highly express MUC1 and PD-L1.

论文信息

作者
Pan J、Zeng W、Jia J、Shi Y、Wang D、Dong J、Fang Z、He J
单位
School of Basic Medical Sciences, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou 510182, China.China
期刊
Vaccines2022 Jul 8
原文标识
PubMed 35891256 · DOI 10.3390/vaccines10071092