Integrating IL-12 mRNA nanotechnology with SBRT eliminates T cell exhaustion in preclinical models of pancreatic cancer.

ABSTRACT: Pronounced T cell exhaustion characterizes immunosuppressive tumors, with the tumor microenvironment (TME) employing multiple mechanisms to elicit this suppression. Traditional immunotherapies, such as immune checkpoint blockade, often fail due to their focus primarily on T cells. To overcome this, we utilized a proinflammatory cytokine, interleukin (IL)-12, that re-wires the immunosuppressive TME by inducing T cell effector function while also repolarizing immunosuppressive myeloid cells. Due to toxicities observed with systemic administration of this cytokine, we utilized lipid nanoparticles encapsulating mRNA encoding IL-12 for intratumoral injection. This strategy has been proven safe and tolerable in early clinical trials for solid malignancies. We report an unprecedented loss of exha

SUBMITTER: Hughson AL 

PROVIDER: S-EPMC11513558 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature