Palomäki Jussi, Kalke Kiira, Orpana Julius, Lund Liisa, Frejborg Fanny, Paavilainen Henrik, Järveläinen Hannu, Hukkanen Veijo
Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland.
Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, 20520 Turku, Finland.
Microorganisms. 2023 Oct 29;11(11):2657. doi: 10.3390/microorganisms11112657.
Herpes simplex virus (HSV) has proven successful in treating human cancer. Since the approval of talimogene laherparepvec (T-VEC) in 2015, HSV has been thoroughly researched to discover novel mechanisms to combat cancer and treat other diseases. Another HSV-based drug, beremagene geperpavec (B-VEC), received approval in 2023 to treat the rare genetic disease dystrophic epidermolysis bullosa, and was also the first clinically approved HSV vector carrying an extracellular matrix (ECM)-modifying transgene. The ECM is a network of macromolecules surrounding cells, which provides support and regulates cell growth and differentiation, the disruption of which is common in cancer. The naked mole rat (NMR) has a thick ECM and a unique mutation in the () gene, which has been linked to the high cancer resistance of the species. To study the effect of this mutation in human cancer, we have developed an attenuated, replication-competent HSV vector expressing the gene. The viral replication, transgene expression and cytotoxic effect of the novel vector was studied in glioma cells. Our results show that an attenuated, replication-competent HSV vector expressing a foreign ECM-modifying transgene, namely , provides an effective tool to study and combat cancer in humans.
单纯疱疹病毒（HSV）已被证明在治疗人类癌症方面取得了成功。自2015年塔利莫基因拉赫帕里韦克（T-VEC）获批以来，人们对HSV进行了深入研究，以发现对抗癌症和治疗其他疾病的新机制。另一种基于HSV的药物贝雷马基因格佩帕韦克（B-VEC）于2023年获批用于治疗罕见的遗传性疾病营养不良性大疱性表皮松解症，它也是首个临床获批的携带细胞外基质（ECM）修饰转基因的HSV载体。ECM是围绕细胞的大分子网络，它提供支持并调节细胞生长和分化，其破坏在癌症中很常见。裸鼹鼠（NMR）具有厚厚的ECM，并且在（）基因中存在独特的突变，这与该物种的高抗癌性有关。为了研究这种突变在人类癌症中的作用，我们开发了一种表达该基因的减毒、有复制能力的HSV载体。在胶质瘤细胞中研究了新型载体的病毒复制、转基因表达和细胞毒性作用。我们的结果表明，一种表达外源ECM修饰转基因即的减毒、有复制能力的HSV载体，为研究和对抗人类癌症提供了一种有效的工具。
