Intratumoral Administration of Recombinant Murine Interleukin‐12 Prevents Tumor Progression and Bone Invasion

OBJECTIVE: Oral squamous cell carcinoma (OSCC) frequently invades the mandibular bone, leading to metastasis and poor prognosis. This study aimed to evaluate the therapeutic effects of locally administered interleukin-12 (IL-12) using an immunocompetent mouse model mimicking the clinical features of mandibular bone invasion. METHODS: The effects of IL-12 on tumor growth and bone resorption were evaluated using subcutaneous and bone invasion models of OSCC in both immunocompetent and athymic mice. Bone resorption was assessed by micro-computed tomography (CT). In addition, quantitative polymerase chain reaction (qPCR) was performed to quantify the expression of osteoclast markers (Acp5, Ctsk) and immune-related genes (Ifng, Fasl). RESULTS: Intratumoral injection of recombinant murine IL-12 (r-mIL-12) significantly prolonged mouse survival and suppressed tumor growth in immunocompetent mice. Micro-CT revealed reduced bone resorption in the r-mIL-12-treated group. Consistently, qPCR demonstrated downregulation of Acp5 and Ctsk, along with upregulation of Ifng and Fasl compared to controls. In contrast, r-mIL-12 treatment had no significant effect on tumor growth or bone resorption in athymic mice, underscoring the importance of T cells in controlling bone invasion. CONCLUSIONS: These findings suggest that local administration of r-mIL-12 may serve as an effective therapeutic approach for OSCC with mandibular bone invasion.