Peritumoral administration of antigen-unstimulated bone marrow-derived dendritic cells inhibits tumour growth

Murine BM cells from B6 mice were grown in vitro in medium supplemented wit h GM-CSF and IL-4 to differentiate DC from DC precursors. After 10 days of culture, approximately 20% of the cell population exhibited the characteris tic morphology of BMDC, In cytofluorometric analysis the morphological chan ges of cells were accompanied by upregulation of the expression of the MAC class II, CD11c, CD80, and CD86 molecules. The BMDC were pulsed with a lysa te of syngeneic MK16 carcinoma cells and used for irt vitro activation of S C. Go-cultivation of the carcinoma lysate-pulsed BMDC with SC induced a pro liferative response of the syngeneic SC. Priming of the proliferative respo nses was more efficient when the BMDC were grown in the presence of GM-CSF and IL-4 for 10 days than for 7 days. The in vivo effect of mature, tumour lysate-unstimulated BMDC was examined in mice carrying syngeneic MK16 carci noma transplants. It has been found that local pretreatment with BMDC inhib its growth of a subsequent challenge inoculum of the MK16 cells. Similarly, treatment of mice carrying small MK16 tumours and of those with MK16 surgi cal minimal residual disease performed with BMDC significantly inhibited tu mour growth. It can be concluded from these results that local concentratio n of mature BR-IDC at the tumour site carl control the development and grow th of the transplanted tumour inoculum.