Abstract A53: Intranasal nanoparticulate PLGA cancer vaccine administration prevents secondary lung metastasis

The lung is one of the most frequent sites of cancer metastasis. Because metastatic lung disease is usually associated with poor survivorship, decreasing secondary lung metastasis will decrease morbidity and mortality associated with cancer. Mitigating tumor immunosurveillance at metastatic sites such as the lung is essential for tumor progression and metastasis. As such, tumors developing elsewhere in the body take advantage of the natural tolerogenicity of the lung to establish immunosuppressive niches via tumor burden induce pre-metastatic niche formation to support lung metastasis. Here we tested the ability of an intranasal nano-vaccine administration to prevent the seeding of tumor cells in the lungs by pre-emptying tumor burden induced immunosuppression. Our hypothesis is that intranasal administration of cancer nano-vaccine will prevent secondary lung metastasis from an existing primary tumor. Because breast cancer is the one of the primary tumors with high propensity to metastasize to the lung, we used the syngeneic mouse breast tumor model to test our hypothesis. Our results showed that intranasal administration of our engineered nano-vaccine protected the lungs of female BALB/c mice from secondary lung metastasis after orthotopic implantation of murine 4T1 tumors. The protection was as a result of nano-vaccine induced antitumor immunity in the lungs. Mice that received the intranasal nano-vaccine had increased frequency of effector T-cells and increase accumulation of lung resident memory T-cell in their lungs. This coincided with increased frequency of IFN-g and granzyme B producing CD8+ T-cells following ex-vivo restimulation of lymphocytes from the lungs of previously immunized mice with tumor cell. These results demonstrate that cancer vaccines can still be part of an integrated cancer therapy where they can be used as a prophylactic approach to prevent secondary lung metastasis. Citation Format: Michael A Donkor, Jamie Choe, Byron Quinn, Harlan P Jones. Intranasal nanoparticulate PLGA cancer vaccine administration prevents secondary lung metastasis [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr A53.