Personalized cancer vaccines are a promising approach for inducing T cell immunity to tumor neoantigens. Using a self-assembling nanoparticle vaccine that links neoantigen peptides to a Toll-like receptor 7/8 agonist (SNP-7/8a), we show how the route and dose alter the magnitude and quality of neoantigen-specific CD8⁺ T cells. Intravenous vaccination (SNP-IV) induced a higher proportion of TCF1⁺PD-1⁺CD8⁺ T cells as compared to subcutaneous immunization (SNP-SC). Single-cell RNA sequencing showed that SNP-IV induced stem-like genes (Tcf7, Slamf6, Xcl1) whereas SNP-SC enriched for effector genes (Gzmb, Klrg1, Cx3cr1). Stem-like cells generated by SNP-IV proliferated and differentiated into effector cells upon checkpoint blockade, leading to superior antitumor response as compared to SNP-SC in a therapeutic model. The duration of antigen presentation by dendritic cells controlled the magnitude and quality of CD8⁺ T cells. These data demonstrate how to optimize antitumor immunity by modulating vaccine parameters for specific generation of effector or stem-like CD8⁺ T cells.

个性化癌症疫苗是一种很有前途的方法，可以诱导 T 细胞对肿瘤新抗原产生免疫。我们使用将新抗原肽与 Toll 样受体 7/8 激动剂 (SNP-7/8a) 连接的自组装纳米颗粒疫苗，展示了途径和剂量如何改变新抗原特异性 CD8 ⁺ T 细胞的量级和质量。与皮下免疫 (SNP-SC) 相比，静脉内疫苗接种 (SNP-IV) 诱导了更高比例的 TCF1 ⁺ PD-1 ⁺ CD8 ^{+ T 细胞。}单细胞 RNA 测序显示 SNP-IV 诱导干细胞样基因（Tcf7、Slamf6、Xcl1），而 SNP-SC 富集效应基因（Gzmb、Klrg1, Cx3cr1 )。在检查点阻断后，由 SNP-IV 产生的干细胞样细胞增殖并分化为效应细胞，与治疗模型中的 SNP-SC 相比，产生了更好的抗肿瘤反应。树突状细胞呈递抗原的持续时间控制着 CD8 ⁺ T 细胞的数量和质量。这些数据证明了如何通过调节疫苗参数来优化抗肿瘤免疫，以产生特定的效应或干细胞样 CD8 ⁺ T 细胞。