Potent antitumor efficacy of human dental pulp stem cells armed with YSCH-01 oncolytic adenovirus
Xu He1, Wei Yao2, Ji-Ding Zhu2
1Department of Stomatology, Huashan Hospital, Fudan University, 12 Urumqi Road, Jing'an District, Shanghai, 200040, China.
Background:
Systemic administration of oncolytic adenovirus for cancer therapy is still a challenge. Mesenchymal stem cells as cell carriers have gained increasing attention in drug delivery due to their excellent tumor tropism, immunosuppressive modulatory effects, and paracrine effects. However, the potential of human dental pulp stem cells (hDPSCs) loaded with oncolytic adenovirus for cancer biotherapy has not been investigated yet.
Methods:
The stemness of hDPSCs was characterized by FACS analysis and Alizarin red staining, Oil Red O staining, and immunofluorescence assays. The biological fitness of hDPSCs loaded with oncolytic adenovirus YSCH-01 was confirmed by virus infection with different dosages and cell viability CCK-8 assays. Additionally, the expression of CAR receptor in hDPSCs was detected by qPCR assay. Tumor tropism of hDPSC loaded with YSCH-01 in vitro and in vivo was investigated by Transwell assays and living tumor-bearing mice imaging technology and immunohistochemistry, Panoramic scanning of frozen section slices assay analysis. Furthermore, the antitumor efficacy was observed through the different routes of YSCH-01/hPDSCs administration in SW780 and SCC152 xenograft models. The direct tumor cell-killing effect of YSCH-01/hDPSCs in the co-culture system was studied, and the supernatant of YSCH-01/hDPSCs inhibited cell growth was further analyzed by CCK-8 assays.
Results:
hDPSCs were found to be susceptible to infection by a novel oncolytic adenovirus named YSCH-01 and were capable of transporting this virus to tumor sites at 1000 VP/cell infectious dosage in vitro and in vivo. Moreover, it was discovered that intraperitoneal injection of hDPSCs loaded with oncolytic adenovirus YSCH-01 exhibited potential anti-tumor effects in both SW780 and SCC152 xenograft models. The crucial role played by the supernatant secretome derived from hDPSCs loaded with YSCH-01 significantly exerted a specific anti-tumor effect without toxicity for normal cells, in both an active oncolytic virus and an exogenous protein-independent manner. Furthermore, the use of hDPSCs as a cell carrier significantly reduced the required dosage of virus delivery in vivo compared to other methods.
Conclusions:
These findings highlight the promising clinical potential of hDPSCs as a novel cell carrier in the field of oncolytic virus-based anti-cancer therapy.
Insights
Human dental pulp stem cells (hDPSCs) effectively carry oncolytic adenovirus YSCH-01 to tumors, demonstrating significant anti-cancer effects with reduced viral dosage. This novel cell-based therapy shows promising clinical potential for cancer treatment.
Area of Science:
- Biomedical Engineering
- Cancer Biology
- Stem Cell Therapy
Background:
- Systemic delivery of oncolytic viruses for cancer therapy faces challenges.
- Mesenchymal stem cells are explored as drug delivery vehicles due to tumor tropism and immunomodulatory effects.
- The utility of human dental pulp stem cells (hDPSCs) loaded with oncolytic adenovirus for cancer biotherapy remains uninvestigated.
Purpose of the Study:
- To investigate the potential of hDPSCs as carriers for oncolytic adenovirus YSCH-01.
- To evaluate the tumor-targeting capabilities and anti-tumor efficacy of YSCH-01-loaded hDPSCs.
- To assess the safety and dosage reduction potential of this cell-based delivery system.
Main Methods:
- Characterization of hDPSCs stemness and CAR receptor expression.
- Assessment of hDPSC infection efficiency and viability with oncolytic adenovirus YSCH-01.
- In vitro and in vivo evaluation of tumor tropism and anti-tumor efficacy in xenograft models.
- Analysis of direct and indirect anti-tumor effects of YSCH-01-loaded hDPSCs.
Main Results:
- hDPSCs efficiently uptake and transport oncolytic adenovirus YSCH-01 to tumor sites.
- Intraperitoneal administration of YSCH-01-loaded hDPSCs demonstrated significant anti-tumor effects in SW780 and SCC152 xenograft models.
- The supernatant from YSCH-01-loaded hDPSCs exhibited specific anti-tumor activity independently of active virus or exogenous proteins, with no observed toxicity to normal cells.
- hDPSCs as a carrier significantly reduced the required in vivo viral dosage.
Conclusions:
- hDPSCs are effective carriers for oncolytic adenovirus YSCH-01, exhibiting potent anti-tumor activity.
- The supernatant secretome of YSCH-01-loaded hDPSCs contributes significantly to the anti-cancer effect.
- hDPSCs represent a promising novel cell-based delivery platform for oncolytic virus therapy in cancer treatment.
