IMMUNOTHERAPY OF METASTASES WITH LYMPHOCYTES TREATED WITH EXOGENOUS RNA IN MICE BEARING B16 MELANOMA

Subline B16-F10, a variant cell line of B16 melanoma, is highly metast atic to the lung when injected intravenously into C57BL/6 mice. This e xperimental metastasis model was used to test the anti-tumor effect of exogenous RNA extracted from the lymphoid organs of immunized animals with B16-F10 cells. This RNA preparation is referred to as B16-RNA. A doptive immunotherapy with lymphocytes treated with B16-RNA was effect ive in reducing significantly the number of pulmonary metastatic nodul es. Lymphocytes incubated with medium alone or with RNA from non-immun ized animals (N-RNA) were used as controls. The ability of B16-RNA in modulating antimetastatic activity of normal lymphocytes is abolished by hydrolysis with KOH. This finding indicates that the integrity of t he polynucleotide chain is essential for the activity of B16-RNA. The anti-tumor effect of lymphocytes treated with B16-RNA was enhanced by incubation with a low dose of interleukin-2 (IL-2). A possible role of the double-stranded RNA dependent protein kinase in this phenomenon i s discussed.