Background: The characteristics of glioblastoma, such as drug resistance during treatment, short patient survival, and high recurrence rates, have made patients with glioblastoma more likely to benefit from oncolytic therapy. Methods: In this study, we investigated the safety of the sindbis virus by injecting virus intravenously and intracranially in mice and evaluated the therapeutic effect of the virus carrying different combinations of IL-12, IL-7, and GM-CSF on glioma in a glioma-bearing mouse model. Results: SINV was autologously eliminated from the serum and organs as well as from neural networks after entering mice. Furthermore, SINV was restricted to the injection site in the tree shrew brain and did not spread throughout the whole brain. In addition, we found that SINV-induced apoptosis in conjunction with the stimulation of the immune system by tumor-killing cytokines substantially suppressed tumor development. It is worth mentioning that SINV carrying IL-7 and IL-12 had the most notable glioma-killing effect. Furthermore, in an intracranial glioma model, SINV containing IL-7 and IL-12 effectively prolonged the survival time of mice and inhibited glioma progression. Conclusions: These results suggest that SINV has a significant safety profile as an oncolytic virus and that combining SINV with cytokines is an efficient treatment option for malignant gliomas.
背景：胶质母细胞瘤具有治疗耐药、患者生存期短及复发率高等特点，这使得胶质母细胞瘤患者更可能从溶瘤病毒疗法中获益。方法：本研究通过在小鼠体内静脉及颅内注射辛德毕斯病毒，探究其安全性，并在荷瘤小鼠模型中评估携带不同白细胞介素-12、白细胞介素-7和粒细胞-巨噬细胞集落刺激因子组合的病毒对胶质瘤的治疗效果。结果：辛德毕斯病毒进入小鼠体内后，可从血清、器官及神经网络中自行清除。此外，该病毒在树鼩大脑中仅限于注射部位，未向全脑扩散。同时，我们发现辛德毕斯病毒诱导的细胞凋亡与肿瘤杀伤性细胞因子对免疫系统的刺激作用相结合，能显著抑制肿瘤发展。值得一提的是，携带白细胞介素-7和白细胞介素-12的辛德毕斯病毒对胶质瘤的杀伤效果最为显著。在颅内胶质瘤模型中，含有白细胞介素-7和白细胞介素-12的辛德毕斯病毒有效延长了小鼠的生存时间并抑制了胶质瘤进展。结论：这些结果表明辛德毕斯病毒作为溶瘤病毒具有显著的安全性，且与细胞因子联用是治疗恶性胶质瘤的有效方案。
Oncolytic Viral Therapy for Glioma by Recombinant Sindbis Virus
肿瘤(癌症)患者之家