The Picornaviral Research Unit, The School of Biomedical Sciences and Pharmacy, Faculty of Health, The University of Newcastle, Newcastle, New South Wales 2300, Australia.
Virol J. 2011 Jan 18;8:22. doi: 10.1186/1743-422X-8-22.
Many RNA viruses are displaying great promise in the field of oncolytic virotherapy. Previously, we reported that the picornavirus Coxsackievirus A21 (CVA21) possessed potent oncolytic activity against cultured malignant melanoma cells and melanoma xenografts in mice. In the present study, we demonstrate that three additional Group A Coxsackieviruses; Coxsackievirus A13 (CVA13), Coxsackievirus A15 (CVA15) and Coxsackievirus A18 (CVA18), also have similar oncolytic activity against malignant melanoma. Each of the viruses grew quickly to high titers in cancer cells expressing ICAM-1 and intratumoral injection of preformed subcutaneous SK-Mel-28 xenografts in mice with CVA13, CVA15 and CVA18 resulted in significant tumor volume reduction.As preexisting immunity could potentially hinder oncolytic virotherapy, sera from stage IV melanoma patients and normal controls were tested for levels of protective antibody against the panel of oncolytic Coxsackieviruses. Serum neutralization assays revealed that 3 of 21 subjects possessed low levels of anti-CVA21 antibodies, while protective antibodies for CVA13, CVA15 and CVA18 were not detected in any sample. Serum from individuals who were seropositive for CVA21 failed to exhibit cross-neutralization of CVA13, CVA15 and CVA18. From these studies it can be concluded that the administration of CVA13, CVA15 or CVA18 could be employed as a potential multivalent oncolytic therapy against malignant melanoma.
许多 RNA 病毒在溶瘤病毒治疗领域显示出巨大的潜力。之前，我们报道过肠道病毒柯萨奇病毒 A21（CVA21）对培养的恶性黑素瘤细胞和小鼠中的黑素瘤异种移植物具有强大的溶瘤活性。在本研究中，我们证明了另外三种 A 组柯萨奇病毒；柯萨奇病毒 A13（CVA13）、柯萨奇病毒 A15（CVA15）和柯萨奇病毒 A18（CVA18）对恶性黑素瘤也具有类似的溶瘤活性。每种病毒在表达 ICAM-1 的癌细胞中迅速生长到高滴度，并且在 CVA13、CVA15 和 CVA18 中，预先形成的皮下 SK-Mel-28 异种移植物的肿瘤内注射导致肿瘤体积显著减小。由于预先存在的免疫可能会阻碍溶瘤病毒治疗，因此测试了来自 IV 期黑色素瘤患者和正常对照者的血清中针对一组溶瘤性柯萨奇病毒的保护性抗体水平。血清中和测定显示，21 名受试者中有 3 名具有低水平的抗 CVA21 抗体，而任何样本中均未检测到针对 CVA13、CVA15 和 CVA18 的保护性抗体。针对 CVA21 呈血清阳性的个体的血清未能表现出对 CVA13、CVA15 和 CVA18 的交叉中和作用。从这些研究可以得出结论，CVA13、CVA15 或 CVA18 的给药可作为针对恶性黑素瘤的潜在多价溶瘤治疗方法。
