Mucosal vaccination with an adenoviral vector vaccine protects against pulmonary breast cancer metastasis by robust induction of tissue-resident memory T-cells in the lung

Abstract The presence of tissue-resident memory T-cells (TRM) in solid tumors positively correlates with an improved overall prognosis and responsiveness to checkpoint inhibitor therapy. Rationally designed vaccine approaches capable inducing antitumor TRM at cancer sites are needed harness the full potential localized immunity tumor Our project aims establish antigen-specific lung by mucosal vaccination adenoviral (Ad) prevent treat metastasis murine 4T1 breast model. We employ Ad serotype 5 vectors encoding for tumor-associated antigens from Mage-b MuLV gp70 intranasal vaccination, supplemented Interleukin-1β-encoding vector specifically boost induction. Indeed, particularly if Ad-IL-1β was co-delivered, established high numbers CD69 +CD103 +lung as shown phenotypic functional analyses combination intravascular staining. Vaccine efficacy evaluated a pseudometastasis model mimicking prophylactic against patients. Local immunization led significant protection pulmonary survival compared non-vaccinated and, notably, intramuscularly immunized mice. By using FTY720 inhibit T-cell circulation upon challenge, we confirmed that crucial contributors efficacy. In conclusion, induction tumor-antigen specific key point local metastasis. Ongoing studies analyze therapeutic use this strategy well its immune inhibition. Supported grants 'Anschubfinanzierung (ELAN) im IZKF' 'Doktor Robert Pfleger-Stiftung'.