The therapeutic effect of thermo-sensitive hydrogel loaded with recombinant mycobacterium smegmatis expressing exogenous IL-15 in abdominal metastasis

Tumor immunotherapy is one of the most promising strategies in cancer treatment. Specifically, intraperitoneal immunotherapy has emerged as a novel approach for dealing with abdominal metastases. Previously, we developed a genetically engineered strain of Mycobacterium smegmatis (Ms-IL15) that expresses the cytokine interleukin-15 (IL15), demonstrating significant anti-tumor effects after intratumoral injection. However, intratumoral infusion might not be feasible in the case of diffuse abdominal metastases, making intraperitoneal injection a preferred option.In this study, we developed a bacterial delivery system by incorporating Ms-IL15 into Poloxamer 407, an injectable thermosensitive hydrogel, for intraperitoneal administration. A murine model of peritoneal metastasis was established, and tumor-bearing mice were administered P407/Ms-IL15 once weekly for two consecutive weeks. The anti-tumor efficacy and alterations in the tumor immune microenvironment were systematically evaluated.Intraperitoneal injection of this system exhibited a remarkable tumor-suppressive effect, significantly prolonging the survival of treated mice. Flow cytometric analysis of the tumor immune microenvironment revealed enhanced maturation and activation of dendritic cells (DC), an increased proportion of effector memory T cells and Granzyme B, and suppressed macrophage polarization towards the M2 phenotype.Our findings indicate that a hydrogel-based bacterial delivery system is a safe and effective approach for the treatment of abdominal metastases.