Department of Medical Oncology/Laboratory of Medical and Molecular Oncology (LMMO), Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium.
Neuro-Aging and Viro-Immunotherapy (NAVI) Research Group, Vrije Universiteit Brussel (VUB), Brussels, Belgium.
Front Immunol. 2021 Oct 28;12:733506. doi: 10.3389/fimmu.2021.733506. eCollection 2021.
T-VEC, a HSV-1 derived oncolytic virus, is approved for the treatment of advanced melanoma. The mechanisms that underly the systemic anti-tumor effect that is seen following intratumoral injection have not yet been studied but are likely to be mediated by myeloid dendritic cells (myDC) that initiate an adaptive immune response. In this study we could demonstrate that T-VEC is non-toxic for human myDC. T-VEC and a T-VEC oncolysate of melanoma cell lines were able to mature human myDC. myDC were able to take up lysed melanoma cells and cross-present melanoma-derived tumor antigens to antigen-specific T cells. Our results support the possible role of myDC as mediators of an adaptive anti-tumor effect and intratumoral co-administration of T-VEC plus autologous myDC could be a complementary treatment option. A clinical trial that investigates this hypothesis is currently ongoing.
T-VEC，一种源自单纯疱疹病毒 1 型的溶瘤病毒，已被批准用于治疗晚期黑色素瘤。瘤内注射后观察到的全身性抗肿瘤作用的机制尚未得到研究，但可能是由髓样树突状细胞（myDC）介导的，myDC 会引发适应性免疫反应。在这项研究中，我们能够证明 T-VEC 对人源性 myDC 没有毒性。T-VEC 和黑色素瘤细胞系的 T-VEC 溶瘤物能够使人类 myDC 成熟。myDC 能够摄取裂解的黑色素瘤细胞，并将黑色素瘤衍生的肿瘤抗原交叉呈递给抗原特异性 T 细胞。我们的结果支持了 myDC 作为适应性抗肿瘤作用的介导物的可能作用，并且 T-VEC 联合自体 myDC 的瘤内共给药可能是一种互补的治疗选择。目前正在进行一项临床试验来研究该假说。
