Basic research for antitumor immune response induced by dendritic cells pulsed with lysate of HSV-1-infected tumor cells

本研究将溶瘤单纯疱疹病毒作为治疗恶性脑肿瘤的一种新方法，研究比单纯使用肿瘤抗原致敏的树突状细胞更有效地激活肿瘤抗原的方法，获得共刺激受体的刺激以及将肿瘤抗原呈递给MHC I分子对于抗肿瘤作用的重要性。为了使T淋巴细胞识别肿瘤抗原，MHC II类蛋白也必须伴随加工的肿瘤抗原。建立了A/J小鼠神经母细胞瘤细胞系Neuro 2a和N18的皮下肿瘤模型。我们使用A/J小鼠的骨髓来源的树突状细胞，以确认诱导抗肿瘤免疫应答。结果，通过用T-01（HSV-1）感染的Neuro 2a肿瘤细胞的裂解物脉冲这些树突细胞没有诱导抗肿瘤免疫应答。然而，我们成功地诱导抗肿瘤免疫反应的树突状细胞脉冲与N18肿瘤细胞。

In this study, we used oncolytic herpes simplex viruses as a new treatment for malignant brain tumors, researching methods to activate a tumor antigen more effectively than only using dendritic cells pulsed with a tumor antigen in tumor lysate.For anti-tumor effect, it is important to get co-stimulation acceptor stimulation as well as presenting tumor antigens to MHC I molecule. In order for T-lymphocytes to recognize the tumor antigen, MHC class II protein must also accompany the processed tumor antigen. We made subcutaneous tumor model of Neuro 2a and N18, neuroblastoma cell line of A/J mice. We used bone marrow-derived dendritic cells from A/J mice in order to confirm induction of antitumor immune response. As a result, antitumor immune response did not induced by pulsing these denciritic cells with lysate of T-01(HSV-1)-infected Neuro 2a tumor cells. However, we succeeded in induction of antitumor immune response by dendritic cells pulsed with N18 tumor cells.