Intraperitoneal administration of cationic liposomes containing a TLR3 agonist recruits type I conventional dendritic...

Therapeutic vaccines capable of eliciting CD8 T cell responses are a promising approach in cancer, but the magnitude of immune responses to peptide-based vaccine technologies has so far been modest in humans. The cationic liposome adjuvant CAF®09b has recently shown promising results in clinical trials, where it is administered intraperitoneally (i.p.), as preclinical studies demonstrated superior CD8 T cell responses when using this route compared to subcutaneous delivery.

Exploring the mechanism of CAF09b in mice we investigated biodistribution of the adjuvant and associated antigen in murine studies. We further examined local innate cell recruitment and CD8 T cell responses in the peritoneal cavity.

We observed that i.p. injected CAF09b associated with visceral fatty tissues and created a vaccine depot in the peritoneal cavity. This led to recruitment of BATF3-dependent conventional type I dendritic cells (cDC1) displaying a migratory cDC1 phenotype (CD11c⁺XCR1⁺CD103⁺). Gene ontology analysis further revealed similarities with visceral adipose tissue DCs. CAF09b injection i.p. led to early priming of CD8 T cells localized to the peritoneal cavity and this response was resistant to FTY720 treatment.

This study demonstrates that adjuvants can facilitate recruitment of cDC1s to the peritoneal cavity, a feature that may contribute to the effectiveness of i.p. administration on elicitation of CD8 T cell responses. Furthermore, we demonstrate that CAF09b-induced CD8 T cell responses require BATF3-dependent cDC1 cells. Understanding cDC1 and CD8 T cell dynamics via different immunization routes may aid in the design of more effective vaccine strategies.

This work was primarily supported by the Danish Research Council (FTP fund no. 9041-00131b).