D-K6L 9 peptide combination with IL-12 inhibits the recurrence of tumors in mice.

D-K6L9 peptide is bound by phosphatidylserine and induces necrosis in cancer cells. In our therapeutic experience, this peptide, when administered directly into B16-F10 murine melanoma tumors, inhibited their growth. Cessation of therapy results, however, in tumor relapse. We aimed at developing a combined therapy involving D-K6L9 and additional factors that would yield complete elimination of tumor cells in experimental animals. To this purpose, we employed glycyrrhizin, an inhibitor of HMGB1 protein, BP1 peptide and interleukin (IL)-12. Glycyrrhizin or BP1, when combined with D-K6L9, inhibits growth of primary tumors only during the period of their administration. A long-term tumor growth inhibitory effect was obtained only in combining D-K6L9 with IL-12. At 2 months following therapy cessation, 60 % of animals were alive. Prolonged survival was noted in mice bearing B16-F10 tumors as well as in mice bearing C26 colon carcinoma tumors.