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

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

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.

Keywords: carrier cells; human head and neck squamous cell carcinoma; human mesenchymal stromal cells; mesenchymal stem cells; migration; oncolytic adenovirus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae
  • Adenoviruses, Human*
  • Animals
  • Cell Line, Tumor
  • Head and Neck Neoplasms* / therapy
  • Humans
  • Mesenchymal Stem Cells*
  • Mice
  • Squamous Cell Carcinoma of Head and Neck / therapy

Grants and funding

The work was supported by the German Federal Ministry of Education and Research (BMBF) and the Federal States of Germany Grant “Innovative Hochschule” (FKZ 3IHS024D). Parts of this research were funded by the 7th Framework Programme of the European Commission (project title REBORNE, grant agreement number 241879), the H2020 Programme of the European Commission (project title ADIPOA-2, grant agreement number 643809), and by the Sanitätsakademie der Bundeswehr E/U2AD/ID018/IF557. The materials presented and views expressed here are the responsibility of the authors only. The EU Commission takes no responsibility for any use made of the information set out.