Abstract
To enhance the efficacy of local irradiation of malgnancies, it is important to induce inflammation and to recruit tumor specific T cells and dendritic cells (DC) at cancer sites. Macrophage inflammatory protein 1 alpha(MIP-1 alpha,CCL3)is a chemoattractant for DCs, monocytes and lymphocytes, and have a crucial role in development of inflammation and immune response. We studied the effect of MIP-1 alpha derivative, eMIP (formerly called BB10010) on irradiated subcutaneous tumor in mice. Mice were subcutaneously implanted with Lewis lung carcinoma cells in the right flank. When the diameter of solid tumor reached approximately 1cm, local tumor irradiation with 6 Gy was applied. After 24 h, the mice were received eMIP intravenously. Since then, eMIP was administrated once a week. The effect of irradiation and eMIP was evaluated by measuring the tumor volume.Radiation with 6Gy reduced the tumor volume by 50%, and administration of eMIP enhanced the efficacy of radiation by further 30 % (total reduction rate:80%). The optimal dose of eMIP was 2~5 microgram/mouse in combination with radiation at 6Gy, and eMIP did not have anti-tumor activity by itself in this system. The tumor treated with both radiation and eMIP showed marked infiltration of CD4 and F4/80 positive cells and a slight increase of CD8 positive cells compared with control and radiation-treated group. The results indicate that eMIP enhances the radiation induced inflammatory response and/or tumor specific immune reaction in tumor, and this might be a new approach in the radiation therapy.
