电穿孔介导的新型白蛋白融合 Flt3L DNA 递送促进 cDC1 相关抗癌免疫

Dendritic cells (DCs) constitute a distinct type of immune cell found within tumors, serving a central role in mediating tumor antigen-specific immunity against cancer cells. Frequently, DC functions are dysregulated by the immunosuppressive signals present within the tumor microenvironment (TME). Consequently, DC manipulation holds great potential to enhance the cytotoxic T cell response against cancer diseases.

One strategy involves administering Fms-like tyrosine kinase receptor 3 ligand (Flt3L), a vitally important cytokine for DC development. In this current study, the electroporation-mediated delivery of a novel albumin-fused Flt3L DNA (alb-Flt3L DNA) demonstrated the ability to induce an anti-tumor immune response. This albumin fusion construct possesses more persistent bioactivity in targeted organs.

Furthermore, TC-1-bearing-C57BL/6 mice receiving alb-Flt3L DNA treatment presented better tumor control and superior survival. Cellular analysis revealed that alb-Flt3L DNA administration promoted robust DC and cDC1 expansion.

In addition, increased levels of IFN-γ-secreting CD8 + lymphocytes were found in correlation to greater cDC1 population.

Moreover, the toxicity of alb-Flt3L administration is limited. Collectively, our data showcases a novel DC-based immunotherapy using electroporation to administer alb-Flt3L DNA.