49th Annual International Herpesvirus Workshop 2

My poster ”HSV VECTOR EXPRESSING A VARIANT OF HAS2 GENE EXHIBITS ENHANCED ONCOLYTIC EFFECT AND TUMOR SUPPRESSOR RESPONSE” is presented at the 49th Annual International Herpesvirus Workshop Conference at Berlin, Germany 27. July 2025.

The naked mole rat (NMR) has a long lifespan and low cancer incidence, which are linked to high molecular weight hyaluronan (HMW-HA), produced by a uniquely mutated hyaluronan synthesis 2 (HAS2) protein. To study the anti-cancer mechanism of the mutated has2 gene, we developed an attenuated replication competent HSV vector expressing the NMR-has2 gene and showed that our HSV vector causes a markedly enhanced oncolytic effect on U373MG astrocytoma cells compared to other attenuated HSV vectors and a series of wild type HSV strains [1].

In our recent study, we infected U373MG cells in T-25 bottles and 6-well plates with 1 pfu/cell and U373MG xenografts in ovo with 0.1 – 0.25 * 10⁶ pfu of an HSV vector expressing the NMR-has2 gene. We collected the cells and growth medium at 48 hours post infection (hpi). HA levels from the growth medium were measured by sandwich-type enzyme linked sorbent assay (ELSA) and HA size determination was performed using chromatography. p53 gene expression was measured with RT-qPCR. The sizes of the tumor xenografts were measured at 72 hpi.

Our results show that this HSV vector causes over 70 % increase in the production of HMW-HA, concomitantly elevating p53 expression two-fold in U373MG cells. The vector also seems to be capable of suppressing tumor xenograft growth in ovo. At 72 hours post infection (hpi), the mean tumor size of the U373MG xenografts infected with the HSV vector expressing the NMR-has2 gene was less than 50 % compared to the tumors infected with a control virus (p = 0.005) as well as non-infected tumors (p = 0.004).

In conclusion, our studies highlight the potential of using HSV to utilize the anti-cancer mechanism of the NMR in human cancer.

https://www.herpesvirusworkshop.com/2025/agenda

References

1. Palomäki, J., Kalke, K., Orpana, J., Lund, L., Frejborg, F., Paavilainen, H., Järveläinen, H., & Hukkanen, V. (2023). Attenuated Replication-Competent Herpes Simplex Virus Expressing an ECM-Modifying Transgene Hyaluronan Synthase 2 of Naked Mole Rat in Oncolytic Gene Therapy. Microorganisms, 11(11), 2657. [doi]
2. Palomäki, J., Hukkanen, V., & Järveläinen, H. (2024). Kaljumyyrikön syöpäresistenssi ja sen sovellutusmahdollisuudet tulevaisuuden lääkekehityksessä. Solubiologi, 2024(2), 14–21. [www]
3. Kalke, K., Orpana, J., Lasanen, T., Esparta, O., Lund, L. M., Frejborg, F., Vuorinen, T., Paavilainen, H., & Hukkanen, V. (2022). The In Vitro Replication, Spread, and Oncolytic Potential of Finnish Circulating Strains of Herpes Simplex Virus Type 1. Viruses, 14(6). [doi]