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.
Center for Translational Research and Molecular Biology of Cancer, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeże Armii Krajowej 15, 44-101, Gliwice, Poland, tcichon@io.gliwice.pl.
Tomasz
T
Cichoń
Ryszard
R
Smolarczyk
Sybilla
S
Matuszczak
Magdalena
M
Barczyk
Magdalena
M
Jarosz
Stanisław
S
Szala
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002277:Carcinoma / Q000276:immunology / Q000628:therapy*; D048708:Cell Growth Processes / Q000187:drug effects; D003110:Colonic Neoplasms / Q000276:immunology / Q000628:therapy*; D005260:Female; D019695:Glycyrrhizic Acid / Q000008:administration & dosage; D006801:Humans; D018664:Interleukin-12 / Q000008:administration & dosage; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010446:Peptide Fragments / Q000008:administration & dosage*; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry; D012008:Recurrence; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy*; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects
D000893:Anti-Inflammatory Agents; C000596940:D-K6L9 peptide; D010446:Peptide Fragments; D010455:Peptides; D018664:Interleukin-12; D019695:Glycyrrhizic Acid