Department of Surgery, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
Mol Ther. 2013 Mar;21(3):620-8. doi: 10.1038/mt.2012.257. Epub 2012 Dec 11.
The combination of an oncolytic virus, that directly destroys tumor cells and mediates an acute immune response, with an immune cell therapy, capable of further enlisting and enhancing the host immune response, has the potential to create a potent therapeutic effect. We have previously developed several strategies for optimizing the delivery of oncolytic vaccinia virus vectors to their tumor targets, including the use of immune cell-based carrier vehicles and the incorporation of mutations that increase production of the enveloped form of vaccinia (extracellular enveloped viral (EEV)) that is better adapted to spread within a host. Here, we initially combine these approaches to create a novel therapeutic, consisting of an immune cell (cytokine-induced killer, CIK) preloaded with an oncolytic virus that is EEV enhanced. This resulted in direct interaction between the viral and immune cell components with each assisting the other in directing the therapy to the tumor and so enhancing the antitumor effects. This effect could be further improved through CCL5 expression from the virus. The resulting multicomponent therapy displays the ability for synergistic crosstalk between components, so significantly enhancing tumor trafficking and antitumor effects.
溶瘤病毒直接破坏肿瘤细胞并介导急性免疫反应，与能够进一步招募和增强宿主免疫反应的免疫细胞疗法相结合，具有产生强大治疗效果的潜力。我们之前已经开发了几种将溶瘤痘苗病毒载体递送至其肿瘤靶标的优化策略，包括使用免疫细胞为基础的载体和增加包膜形式（细胞外包膜病毒（EEV））产生的突变，从而更好地适应在宿主内传播。在这里，我们最初将这些方法结合起来，创建了一种新型治疗方法，由预先加载了 EEV 增强的溶瘤病毒的免疫细胞（细胞因子诱导的杀伤细胞，CIK）组成。这导致病毒和免疫细胞成分之间的直接相互作用，彼此相互协助将治疗靶向肿瘤，从而增强抗肿瘤作用。通过病毒从 CCL5 的表达可以进一步提高这种效果。由此产生的多组分治疗显示出组分之间协同相互作用的能力，从而显著增强肿瘤转移和抗肿瘤作用。
