Oncolytic viruses have shown excellent safety profiles in preclinical and clinical studies; however, in most cases therapeutic benefits have been modest. We have previously reported the generation of a chimeric poxvirus (CF33), with significantly improved oncolytic characteristics, through chimerization among different poxviruses. Here we report the sequence analysis of CF33 and oncolytic potential of a GFP-encoding CF33 virus (CF33-GFP) with a J2R deletion in lung cancer models. Replication of CF33-GFP and the resulting cytotoxicity were higher in cancer cell lines compared to a normal cell line, in vitro. After infection with virus, cancer cells expressed markers for immunogenic cell death in vitro. Furthermore, CF33-GFP was safe and exerted potent anti-tumor effects at a dose as low as 1000 plaque forming units in both virus-injected and un-injected distant tumors in A549 tumor xenograft model in mice. Likewise, in a syngeneic model of lung cancer in mice, the virus showed significant anti-tumor effect and was found to increase tumor infiltration by CD8+ T cells. Collectively, these data warrant further investigation of this novel chimeric poxvirus for its potential use as a cancer bio-therapeutic.

中文翻译：

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具有 J2R（胸苷激酶）缺失的嵌合痘病毒在肺癌模型中显示出安全性和抗肿瘤活性。

溶瘤病毒在临床前和临床研究中显示出极好的安全性；然而，在大多数情况下，治疗效果不大。我们之前曾报道过通过不同痘病毒之间的嵌合化产生了具有显着改善的溶瘤特性的嵌合痘病毒 (CF33)。在这里，我们报告了肺癌模型中 CF33 的序列分析和具有 J2R 缺失的 GFP 编码 CF33 病毒（CF33-GFP）的溶瘤潜力。在体外，与正常细胞系相比，癌细胞系中 CF33-GFP 的复制和由此产生的细胞毒性更高。感染病毒后，癌细胞在体外表达免疫原性细胞死亡的标志物。此外，CF33-GFP 是安全的，在小鼠 A549 肿瘤异种移植模型中，在注射病毒和未注射的远处肿瘤中，低至 1000 个斑块形成单位的剂量即可发挥有效的抗肿瘤作用。同样，在小鼠肺癌的同基因模型中，该病毒显示出显着的抗肿瘤作用，并被发现增加了 CD8+ T 细胞的肿瘤浸润。总的来说，这些数据保证了对这种新型嵌合痘病毒作为癌症生物治疗剂的潜在用途的进一步研究。