IL-17-polarizing Vaccination Targeting MUC1 for the Prevention of Lung Cancer
Technical Report,01 Aug 2017,31 Jul 2019
Medical University of South Carolina Charleston United States
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Lung cancer disproportionately affects United States Veterans with rates of disease nearly double to those found in the general population. Immunosurveillance, whereby an effective immune response can detect and eliminate abnormal cells before they progress to invasive malignancy, provides rationale for the development of a prophylactic vaccination regimen. Herein, we developed an adenoviral-based vaccination delivering MUC1 tumor-associated antigen and the immuno stimulatory molecule ICOS-L to induce a unique subset of effector T cells, IL-17-producing CD4 T cells, termed Th17s, shown to have superior antitumor reactivity. As peripheral tolerance limits the induction of immunity to self-derived tumor antigens, we have examined the ability to enhance vaccine immunogenicity through the ablation of regulatory T cells Tregs prior to immunization. We have illustrated that ICOS-L augmented vaccination significantly enhances Th17, but not Tc17 immune responses against MUC1. We further demonstrate that ablation of Tregs prior to immunization increases both cellular and humoral vaccine-induced immunity against MUC1. Preventative vaccination alters the results in greater accumulation of subsets of T cells within pulmonary tumors, with increased CD8 T cells and myeloid cells associated with tumor inhibition and progression, respectively. Collectively, these studies represent a novel strategy for the prevention of lung cancer.
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