Abstract
Abstract PURPOSE: During the last decades, irradiation is one of the most well-known therapies in head and neck cancer. The combination of radiation with other treatment modalities has been researched to improve its therapeutic efficacy and reduce its side effects. Gx-051, that is mesenchymal stem cell (MSC) expressing modified interleukin-12 (MSCs/IL-12M), is recently reported as a novel component of human immune system to attack cancer cells by the recruitment of immune cells with a high specificity. We would like to evaluate the therapeutic benefits of combined radiation and immunotherapy, compared to the treatment with each single modality in allograft animal model. METHODS AND MATERIALS: AT-84 cells, one of murine head and neck carcinoma cells, were injected for allograft induction on C3H/HeN mice. All the mice were randomly divided into 4 groups; control (non-treated), radiation only-treated, Gx-051 only-treated, and irradiation with Gx-051-treated. Intra-tumoral injection of Gx-051 (adopted within 24hr after irradiation) as well as 8 Gy-local irradiation was carried out, totally 4 times (twice a week for 2 weeks). To clarify the anti-tumoral effect of radiation with Gx-051 administration, we provided reasonable evidences; tumor volume, levels of IL-12 and IFN-r, and the changes in signaling pathway related-protein expression level. RESULTS: In vivo allograft study using AT-84 cells and C3H/HeN mice showed that combined treatment with radiation and Gx-051 significantly enhanced the anti-tumor effect. The tumor volume markedly decreased in the combined treatment group compared to other groups (p<0.05). Both levels of IL-12 and IFN-r were significantly higher in the combined treatment group (p<0.05). The expression of Ki-67, p16, and vascular endothelial growth factor were suppressed and that of caspase-3 was enhanced in combined treatment group compared to others in immunostaining. In addition, The protein level of Ras and HIF-1α were reduced and that of cyclin B1 was increased compared to others in immunoblotting. CONCLUSIONS: Our results demonstrated the combined treatment with radiation and Gx-051 enhanced the responses to HNSCC by AT-84 via increasing cytokines’ levels (IL-12 and IFN-r) and mediating signaling pathways (apoptosis, cell cycle, and angiogenesis). Dual administration of radiation with Gx-051 showed significant anti-tumoral effects by inducing apoptosis and inhibiting angiogenesis of tumor cell and these evidences gave us the partial rationale to the further study about the combined therapy of radiation with Gx-051 for the advanced treatment of human HNSCC. This study was supported by grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare (A091205) and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2011-0012555). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-371. doi:1538-7445.AM2012-LB-371
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