Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Swim Across America-Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Mol Ther. 2018 Apr 4;26(4):1008-1019. doi: 10.1016/j.ymthe.2018.01.019. Epub 2018 Jan 31.
Anti-viral immunity presents a major hurdle for systemically administered oncolytic viruses (OV). Intratumoral OV therapy has a potential to overcome this problem through activation of anti-tumor immune response, with local and abscopal effects. However, the effects of anti-viral immunity in such a setting are still not well defined. Using Newcastle Disease Virus (NDV) as a model, we explore the effects of pre-existing anti-viral immunity on therapeutic efficacy in syngeneic mouse tumor models. Unexpectedly, we find that while pre-existing immunity to NDV limits its replication in tumors, tumor clearance, abscopal anti-tumor immune effects, and survival are not compromised and, on the contrary, are superior in NDV-immunized mice. These findings demonstrate that pre-existing immunity to NDV may increase its therapeutic efficacy through potentiation of systemic anti-tumor immunity, which provides clinical rationale for repeated therapeutic dosing and prompts investigation of such effects with other OVs.
抗病毒免疫是全身性给药的溶瘤病毒（OV）的主要障碍。肿瘤内 OV 治疗有可能通过激活抗肿瘤免疫反应，产生局部和远隔效应来克服这个问题。然而，在这种情况下，抗病毒免疫的作用仍未得到很好的定义。我们使用新城疫病毒（NDV）作为模型，研究了预先存在的抗病毒免疫对同种异体小鼠肿瘤模型治疗效果的影响。出乎意料的是，我们发现，虽然预先存在的抗 NDV 免疫限制了其在肿瘤中的复制，但肿瘤清除、远隔抗肿瘤免疫效应和存活率并没有受到影响，相反，在 NDV 免疫小鼠中则更优。这些发现表明，预先存在的抗 NDV 免疫可能通过增强全身抗肿瘤免疫来提高其治疗效果，这为重复治疗剂量提供了临床依据，并促使对其他 OV 进行此类效应的研究。
