肿瘤细胞治疗研究
英文原题：Arming oncolytic herpes simplex virus with CXCL-11, IL-12 and a single-chain antibody against PD-1 to enhance CAR-T cell therapy in pancreatic ductal adenocarcinoma.
我们的数据表明，oHSV30 可能是 PDAC 中 CAR-T 疗法的一种有前景的佐剂。
胰腺导管腺癌（PDAC）是胰腺癌的主要形式，预后极差，迫切需要有效的治疗方法。CAR-T（CAR-T）细胞疗法是一种潜在的治疗途径，但常受到多种因素的制约，包括免疫抑制性微环境、有限的肿瘤浸润、抗肿瘤活性有限以及T细胞持续性短暂。在此，我们构建了一种表达CXCL-11、IL-12和抗PD-1单链抗体的溶瘤单纯疱疹病毒（命名为oHSV30），以增强CAR-T细胞在肿瘤微环境中的浸润、细胞毒性和持续性，从而提高其治疗效果。在免疫健全和免疫缺陷的同基因PDAC模型中，我们证明CAR-T细胞与瘤内给予oHSV30的联合治疗显著降低了肿瘤负荷，并延长了荷瘤小鼠的生存期。总体而言，我们的数据表明，oHSV30可作为PDAC中CAR-T疗法的一种有前景的佐剂。
Pancreatic ductal adenocarcinoma (PDAC), the primary form of pancreatic cancer, has a very poor prognosis and urgently requires effective treatments. Chimeric antigen receptor T (CAR-T) cell therapy presents a potential treatment approach, yet it is often hindered by several factors, including an immunosuppressive microenvironment, limited tumour infiltration, modest anti-tumour activity and short-term T cell persistence. Here, we engineered an oncolytic herpes simplex virus expressing CXCL-11, IL-12 and a single-chain antibody against PD-1 (named oHSV30) to enhance CAR-T cell infiltration, cytotoxicity and persistence in the tumour microenvironment, thereby improving its therapeutic efficacy. In both immunocompetent and immunodeficient syngeneic PDAC models, we demonstrated that the combination of CAR-T cells with the intratumoural administration of oHSV30 significantly reduced tumour burden and prolonged the survival of tumour-bearing mice. Overall, our data suggest that oHSV30 can be a promising adjuvant for CAR-T therapy in PDAC.
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