Intratumoral Injection of Engineered Induces Antitumor Immunity and Inhibits Tumor Growth.

Conventional type 1 dendritic cells are essential for antigen presentation and successful initiation of antitumor CD8 T cells. However, their abundance and function within tumors tend to be limited. , a fast-growing, nonpathogenic mycobacterium, proves to be easily modified with synthetic biology. Herein, we construct an engineered expressing a fusion protein of Fms-like tyrosine kinase 3 ligand and costimulator CD40darpin (rM-FC) since the 2 drugs are reported to have a good synergistic effect. Intratumoral delivery of rM-FC effectively recruits and activates dendritic cells (DCs), especially CD103 DCs and CD80CD86 DCs, further inducing sufficient migration of effector memory T cells into the tumor microenvironment. This successfully converts the so-called immune-desert tumors to the "hot" phenotype. In B16F10 mouse melanoma tumor models, local injection of rM-FC into the primary tumor triggers a robust T cell immune response to restrain the growth of both the treated tumors and the distant untreated ones. The population of PDL1 tumor cells increased after the in situ vaccination, and murine tumors became more responsive to programmed death ligand 1 (PDL1) blockade, prompting the combination therapy. Overall, our findings demonstrate that rM-FC acts as a strong DC agonist and remarkably enhances antitumor immunity.