通过靶向肿瘤相关巨噬细胞的嵌合受体工程化溶瘤病毒重振内源性抗肿瘤免疫
Rejuvenating endogenous antitumor immunity via a chimeric receptor-engineered oncolytic virus targeting tumor-associated macrophages.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
装载携带核心蛋白聚糖的溶瘤腺病毒的间充质干细胞对乳腺癌肺转移小鼠模型的治疗作用
英文原题：Therapeutic effects of mesenchymal stem cells loaded with oncolytic adenovirus carrying decorin on a breast cancer lung metastatic mouse model.
查看英文原题
Therapeutic effects of mesenchymal stem cells loaded with oncolytic adenovirus carrying decorin on a breast cancer lung metastatic mouse model.
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中文摘要
溶瘤腺病毒（OAds）是肿瘤的替代免疫治疗策略。然而，肝脏摄取和抗体中和是治疗肿瘤转移过程中全身递送的两个主要障碍。间充质干细胞（MSCs）已成为改善递送的潜在载体。
在本研究中，我们将表达decorin的OAds（rAd.DCN）或不含外源基因的OAds（rAd.Null）负载到脐带来源的MSCs（UC-MSCs）中，用于治疗乳腺癌肺转移。在体内，与其它组相比，rAd.Null、MSCs.Null和rAd.DCN在小鼠模型中表现出抗肿瘤效果。出乎意料的是，MSCs.Null比MSCs.DCN表现出更强的抗肿瘤反应，包括改善生存率和减少肿瘤负荷。与rAd.Null相比，MSCs.Null和MSCs.DCN均能改善病毒在肺部转移性肿瘤病灶中的扩散和分布。MSCs.DCN在肺中产生的decorin远多于rAd.DCN；然而，rAd.DCN对decorin下游靶基因的降低作用远强于MSCs.DCN，这与体外实验结果一致。
此外，rAd.DCN、MSCs.Null和MSCs.DCN能够降低肺中的细胞因子水平。总之，MSCs改善了溶瘤腺病毒在肿瘤组织中的递送和扩散，并增强了治疗效果。
然而，MSCs.DCN降低了OAd引发的抗肿瘤反应，可能通过接触依赖性机制。
展开英文摘要原文
Oncolytic adenoviruses (OAds) are alternative immune therapeutic strategies for tumors.
However, liver uptake and antibody neutralization are two major barriers for systemic delivery during the treatment of tumor metastasis. Mesenchymal stem cells (MSCs) have emerged as potential vehicles to improve delivery. In this study, we loaded umbilical-cord-derived MSCs (UC-MSCs) with OAds expressing decorin (rAd. DCN) or without foreign genes (rAd. Null) to treat breast cancer lung metastasis. In vivo , rAd. Null, MSCs. Null, and rAd. DCN exhibited antitumor effects compared with other groups in a mouse model.
Unexpectedly, MSCs. Null showed much greater antitumor responses than MSCs. DCN, including improved survival and reduced tumor burden. Compared with rAd. Null, both MSCs. Null and MSCs. DCN could improve the viral spread and distribution in metastatic tumor lesions in the lung. MSCs. DCN produced much more decorin in lungs than rAd. DCN; however, rAd. DCN reduced the downstream target genes of decorin much more strongly than MSCs. DCN, which was consistent with in vitro findings.
In addition, rAd. DCN, MSCs. Null, and MSCs. DCN could reduce The cytokine levels in the lung.
In conclusion, MSCs improved oncolytic adenoviral delivery and spread in tumor tissues and enhanced therapeutic effects.
However, MSCs. DCN reduced OAd-evoked antitumor responses, possibly via a contact-dependent mechanism.
论文信息
- 作者
- Zhang Y、Liu C、Wang T、Kong F、Zhang H、Yi J、Dong X、Duan H
- 单位
- Department of Experimental Haematology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, P.R. China.China
- 期刊
- Molecular therapy oncolytics2022 Mar 17
- 原文标识
- PubMed 35229027 · DOI 10.1016/j.omto.2022.01.007
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