鼻内初免-加强 RNA 疫苗接种诱导强效 T 细胞应答用于肺癌治疗

The rapid success of RNA vaccines in preventing SARS-CoV-2 has sparked interest in their use for cancer immunotherapy. Although many cancers originate in mucosal tissues, current RNA cancer vaccines are mainly administered non-mucosally.

Here, we developed a non-invasive intranasal cancer vaccine utilizing circular RNA encapsulated in lipid nanoparticles to induce localized mucosal immune responses. This strategy elicited potent anti-tumor T cell responses in preclinical lung cancer models while mitigating the systemic adverse effects commonly associated with intravenous RNA vaccination.

Specifically, type 1 conventional dendritic cells were indispensable for T cell priming post-vaccination, with both alveolar macrophages and type 1 conventional dendritic cells boosting antigen-specific T cell responses in lung tissues.

Moreover, the vaccination facilitated the expansion of both endogenous and adoptive transferred antigen-specific T cells, resulting in robust anti-tumor efficacy. Single-cell RNA sequencing revealed that the vaccination reprograms endogenous T cells, enhancing their cytotoxicity and inducing a memory-like phenotype.

Additionally, the intranasal vaccine can modulate the response of CAR-T cells to augment therapeutic efficacy against tumor cells expressing specific tumor-associated antigens. Collectively, the intranasal RNA vaccine strategy represents a novel and promising approach for developing RNA vaccines targeting mucosal malignancies.