Antibody-Neutralized Reovirus Is Effective in Oncolytic Virotherapy
Antibody-Neutralized Reovirus Is Effective in Oncolytic Virotherapy
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DOI：
10.1158/2326-6066.cir-18-0309
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发表时间：
2018-10-01
影响因子：
10.1
通讯作者：
Ilett, Elizabeth J.
中科院分区：
文献类型：
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作者：
Berkeley, Robert A.;Steele, Lynette R.;Ilett, Elizabeth J.
免疫疗法显示出对其他无法治愈的癌症的希望。溶瘤病毒（OV）作为直接细胞毒性剂开发，通过激活免疫系统介导其抗肿瘤作用。然而，OV也刺激抗病毒免疫应答，包括诱导OV中和抗体。目前的教条表明，患者中预先存在的抗病毒中和抗体的存在或它们在病毒治疗期间的发展是全身OV递送的障碍，使得重复全身治疗无效。然而，我们已经发现，人单核细胞装载有预先形成的呼肠孤病毒抗体复合物，其中呼肠孤病毒被完全中和，将功能性复制呼肠孤病毒递送至肿瘤细胞，导致肿瘤细胞感染和裂解。该递送机制至少部分地由抗体受体（特别是Fc γ RIII）介导，所述抗体受体介导单核细胞对呼肠孤病毒/抗体复合物的摄取和内化。这一发现对溶瘤病毒治疗和临床OV治疗策略的设计具有意义。
Immunotherapy is showing promise for otherwise incurable cancers. Oncolytic viruses (OVs), developed as direct cytotoxic agents, mediate their antitumor effects via activation of the immune system. However, OVs also stimulate antiviral immune responses, including the induction of OV-neutralizing antibodies. Current dogma suggests that the presence of preexisting antiviral neutralizing antibodies in patients, or their development during viral therapy, is a barrier to systemic OV delivery, rendering repeat systemic treatments ineffective. However, we have found that human monocytes loaded with preformed reovirusantibody complexes, in which the reovirus is fully neutralized, deliver functional replicative reovirus to tumor cells, resulting in tumor cell infection and lysis. This delivery mechanism is mediated, at least in part, by antibody receptors (in particular Fc gamma RIII) that mediate uptake and internalization of the reovirus/antibody complexes by the monocytes. This finding has implications for oncolytic virotherapy and for the design of clinical OV treatment strategies.