Enhanced antitumor effect of dendritic cell based immunotherapy after intratumoral injection of radionuclide Ho-166 against B16 melanoma

Abstract

Internal radiotherapy with the intratumoral injection of the beta-emitting radionuclide, Holmium (Ho)-166, into B16 melanoma resulted in a reduction in size and growth rate; however, complete remission was not always achieved. Therefore, additional dendritic cell (DC) therapy was investigated to determine whether it could improve therapeutic results. Malignant melanoma was induced in mice by inoculating B16F10 cell line subcutaneously. Fifty-four mice were divided into four groups: (1) non-treated (group I, n = 11), (2) treated with Ho-166 (group II, n = 16), (3) treated with immature DCs (group III, n = 8), and (4) treated with immature DCs after Ho-166 injection (group IV, n = 19). Changes in tumor size, survival rates, and immunologic profiles were observed. Nineteen days after Ho-166 or PBS injection, mean tumor sizes in the four groups were 6044 ± 1046, 1658 ± 523, 3871 ± 921, and 444 ± 167 mm3, respectively. We observed a significant decrease in tumor size (P < 0.05) and an increase in survival in group IV. When the B16F10 cell line was reinjected into the contralateral backs of survivors, much slower growth was observed in group IV (P < 0.05). Both tumor-specific CTL and natural killer cell activities and the infiltration of inflammatory cells into tumor tissues were found to be elevated in group IV. In addition, strong immune responses as determined by in vitro T cell proliferation, ELISA and ELISPOT assay were induced in group IV. Our results suggest that a combination of internal radiotherapy using Ho-166 and immature DCs could be used either to treat unresectable melanoma or as an adjuvant therapy after surgery.