Knapp Jason P, Kakish Julia E, Bridle Byram W, Speicher David J
Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.
ImmunoCeutica Inc., Cambridge, ON N0B 1B0, Canada.
Biomedicines. 2022 Aug 19;10(8):2024. doi: 10.3390/biomedicines10082024.
The temperature of a solid tumor is often dissimilar to baseline body temperature and, compared to healthy tissues, may be elevated, reduced, or a mix of both. The temperature of a tumor is dependent on metabolic activity and vascularization and can change due to tumor progression, treatment, or cancer type. Despite the need to function optimally within temperature-variable tumors, oncolytic viruses (OVs) are primarily tested at 37 °C in vitro. Furthermore, animal species utilized to test oncolytic viruses, such as mice, dogs, cats, and non-human primates, poorly recapitulate the temperature profile of humans. In this review, we discuss the importance of temperature as a variable for OV immunotherapy of solid tumors. Accumulating evidence supports that the temperature sensitivity of OVs lies on a spectrum, with some OVs likely hindered but others enhanced by elevated temperatures. We suggest that in vitro temperature sensitivity screening be performed for all OVs destined for the clinic to identify potential hinderances or benefits with regard to elevated temperature. Furthermore, we provide recommendations for the clinical use of temperature and OVs.
实体瘤的温度通常与基线体温不同，与健康组织相比，可能会升高、降低或两者兼有。肿瘤的温度取决于代谢活性和血管形成，并且会由于肿瘤进展、治疗或癌症类型而发生变化。尽管需要在温度可变的肿瘤内实现最佳功能，但溶瘤病毒（OVs）主要在体外37°C的条件下进行测试。此外，用于测试溶瘤病毒的动物物种，如小鼠、狗、猫和非人类灵长类动物，无法很好地模拟人类的温度特征。在这篇综述中，我们讨论了温度作为实体瘤OV免疫治疗变量的重要性。越来越多的证据支持，OVs的温度敏感性呈一定范围，一些OVs可能会受到高温的阻碍，而另一些则会因高温而增强。我们建议，对所有即将进入临床的OVs进行体外温度敏感性筛选，以确定高温可能带来的潜在阻碍或益处。此外，我们还提供了关于温度和OVs临床应用的建议。
