T cells have a critical role in mediating antitumour immunity. The success of immune checkpoint inhibitors (ICIs) for cancer treatment highlights how enhancing endogenous T cell responses can mediate tumour regression. However, mortality remains high for many cancers, especially in the metastatic setting. Based on advances in the genetic characterization of tumours and identification of tumour-specific antigens, individualized therapeutic cancer vaccines targeting mutated tumour antigens (neoantigens) are being developed to generate tumour-specific T cells for improved therapeutic responses. Early clinical trials using individualized neoantigen vaccines for patients with advanced disease had limited clinical efficacy despite demonstrated induction of T cell responses. Therefore, enhancing T cell activity by improving the magnitude, quality and breadth of T cell responses following vaccination is one current goal for improving outcome against metastatic tumours. Another major consideration is how T cells can be further optimized to function within the tumour microenvironment (TME). In this Perspective, we focus on neoantigen vaccines and propose a new approach, termed Vax-Innate, in which vaccination through intravenous delivery or in combination with tumour-targeting immune modulators may improve antitumour efficacy by simultaneously increasing the magnitude, quality and breadth of T cells while transforming the TME into a largely immunostimulatory environment for T cells.

T 细胞在介导抗肿瘤免疫中起关键作用。免疫检查点抑制剂 （ICI） 在癌症治疗中的成功凸显了增强内源性 T 细胞反应如何介导肿瘤消退。然而，许多癌症的死亡率仍然很高，尤其是在转移性情况下。基于肿瘤遗传表征和肿瘤特异性抗原鉴定的进展，正在开发针对突变肿瘤抗原（新抗原）的个体化治疗性癌症疫苗，以产生肿瘤特异性 T 细胞以改善治疗反应。尽管已证明可诱导 T 细胞反应，但对晚期疾病患者使用个体化新抗原疫苗的早期临床试验临床疗效有限。因此，通过提高疫苗接种后 T 细胞反应的幅度、质量和广度来增强 T 细胞活性是改善转移性肿瘤结果的当前目标之一。另一个主要考虑因素是如何进一步优化 T 细胞以在肿瘤微环境 （TME） 中发挥作用。在这个观点中，我们专注于新抗原疫苗并提出了一种称为 Vax-Innate 的新方法，其中通过静脉内递送或与靶向肿瘤的免疫调节剂联合接种疫苗可以通过同时增加 T 细胞的大小、质量和广度来提高抗肿瘤疗效，同时将 TME 转化为 T 细胞的主要免疫刺激环境。