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评估人骨髓基质细胞作为携带溶瘤腺病毒 HAdV-5 递送至头颈部鳞状细胞癌的载体。

Evaluation of Human Mesenchymal Stromal Cells as Carriers for the Delivery of Oncolytic HAdV-5 to Head and Neck Squamous Cell Carcinomas.

机构信息

Department of Gene Therapy, University Medical Center Ulm, 89081 Ulm, Germany.

Institute for Transfusion Medicine, University Medical Center Ulm, 89081 Ulm, Germany.

出版信息

Viruses. 2023 Jan 13;15(1):218. doi: 10.3390/v15010218.

DOI:10.3390/v15010218
PMID:36680258
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9864513/
Abstract

Human multipotent mesenchymal stromal cells (hMSCs) are of significant therapeutic interest due to their ability to deliver oncolytic adenoviruses to tumors. This approach is also investigated for targeting head and neck squamous cell carcinomas (HNSCCs). HAdV-5-HexPos3, a recently reported capsid-modified vector based on human adenovirus type 5 (HAdV-5), showed strongly improved infection of both hMSCs and the HNSCC cell line UM-SCC-11B. Given that, we generated life cycle-unmodified and -modified replication-competent HAdV-5-HexPos3 vector variants and analyzed their replication within bone marrow- and adipose tissue-derived hMSCs. Efficient replication was detected for both life cycle-unmodified and -modified vectors. Moreover, we analyzed the migration of vector-carrying hMSCs toward different HNSCCs. Although migration of hMSCs to HNSCC cell lines was confirmed in vitro, no homing of hMSCs to HNSCC xenografts was observed in vivo in mice and in ovo in a chorioallantoic membrane model. Taken together, our data suggest that HAdV-5-HexPos3 is a potent candidate for hMSC-based oncolytic therapy of HNSCCs. However, it also emphasizes the importance of generating optimized in vivo models for the evaluation of hMSC as carrier cells.

摘要

人多能间充质基质细胞（hMSCs）由于其能够将溶瘤腺病毒递送至肿瘤而具有重要的治疗意义。这种方法也被用于针对头颈部鳞状细胞癌（HNSCCs）的靶向治疗。最近报道的基于人腺病毒 5 型（HAdV-5）的衣壳修饰载体 HAdV-5-HexPos3，显示出对 hMSCs 和 HNSCC 细胞系 UM-SCC-11B 的强烈改善的感染能力。鉴于此，我们生成了未经修饰和修饰的复制完整的 HAdV-5-HexPos3 载体变体，并分析了它们在骨髓和脂肪组织来源的 hMSCs 中的复制。两种未经修饰和修饰的载体均检测到有效的复制。此外，我们分析了携带载体的 hMSCs 向不同 HNSCCs 的迁移。尽管在体外证实了 hMSCs 向 HNSCC 细胞系的迁移，但在体内的小鼠和鸡胚的尿囊膜模型中均未观察到 hMSCs 向 HNSCC 异种移植物的归巢。总之，我们的数据表明 HAdV-5-HexPos3 是用于 hMSC 基于 HNSCC 的溶瘤治疗的有效候选者。然而，它也强调了生成优化的体内模型对于评估 hMSC 作为载体细胞的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed91/9864513/8a684615df86/viruses-15-00218-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed91/9864513/a2128d148f42/viruses-15-00218-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed91/9864513/8a684615df86/viruses-15-00218-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed91/9864513/d6742cffff9b/viruses-15-00218-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed91/9864513/429c38da16cc/viruses-15-00218-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed91/9864513/f0f2a76382ad/viruses-15-00218-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed91/9864513/b44f91c649e8/viruses-15-00218-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed91/9864513/24b6c7b58938/viruses-15-00218-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed91/9864513/afd5f6dffe25/viruses-15-00218-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed91/9864513/a2128d148f42/viruses-15-00218-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed91/9864513/8a684615df86/viruses-15-00218-g008.jpg

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