Abstract:
Virus-based tumour vaccines offer many advantages compared to other antigen-delivering systems. They generate concerted innate and adaptive immune response, and robust CD8+ T cell responses. We engineered a non-replicating pseudotyped influenza virus (S-FLU) to deliver the well-known cancer testis antigen, NY-ESO-1 (NY-ESO-1 S-FLU). Intranasal or intramuscular immunization of NY-ESO-1 S-FLU virus in mice elicited a strong NY-ESO-1-specific CD8+ T cell response in lungs and spleen that resulted in the regression of NY-ESO-1-expressing lung tumour and subcutaneous tumour, respectively. Combined administration with anti-PD-1 antibody, NY-ESO-1 S-FLU virus augmented the tumour protection by reducing the tumour metastasis. We propose that the antigen delivery through S-FLU is highly efficient in inducing antigen-specific CD8+ T cell response and protection against tumour development in combination with PD-1 blockade.
摘要:
与其它抗原递送系统相比,基于病毒的肿瘤疫苗提供许多优点。它们产生一致的先天和适应性免疫反应,和强大的CD8+T细胞反应。我们设计了一种非复制型假型流感病毒(S-FLU)来提供众所周知的癌症睾丸抗原,NY-ESO-1(NY-ESO-1S-FLU)。小鼠鼻内或肌内免疫NY-ESO-1S-FLU病毒在肺和脾脏中引起强烈的NY-ESO-1特异性CD8T细胞反应,导致表达NY-ESO-1的肺肿瘤和皮下肿瘤,分别。与抗PD-1抗体联合给药,NY-ESO-1S-FLU病毒通过减少肿瘤转移来增强肿瘤保护。我们提出通过S-FLU的抗原递送在与PD-1阻断组合诱导抗原特异性CD8+T细胞应答和针对肿瘤发展的保护方面是高效的。