PEPTIDES FOR THE TREATMENT OF CANCER ASSOCIATED WITH THE HUMAN PAPILOMA VIRUS (HPV) AND OTHER EPITHELIAL TUMOURS

摘要

11 specific peptides (A), also their homologous variants and mimetics produced by synthetic or recombinant methods, that bind to the phosphorylation site of casein kinase II, are new. 11 specific peptides (A), of formulae (1)-(11) also their homologous variants and mimetics produced by synthetic or recombinant methods, that bind to the phosphorylation site of casein kinase II, are new. (1) Cys-Ser-Val-Arg-Gln-Gly-Pro-Val-Gln-Lys-Cys; (2) Cys-Ser-Ser-Cys-Gln-Asn-Ser-Pro-Ala-Leu-Cys; (3) Cys-Gln-Ile-Pro-Gln-Arg-Thr-Ala-Thr-Arg-Cys; (4) Cys-Ala-Lys-Gln-Arg-Thr-Asp-Pro-Gly-Tyr-Cys; (5) Cys-Trp-Met-Ser-Pro-Arg-His-Leu-Gly-Thr-Cys; (6) Cys-Arg-Asn-Cys-Thr-Val-Ile-Gln-Phe-Ser-Cys; (7) Cys-His-Tyr-Ile-Ala-Gly-Thr-Val-Gln-Gly-Cys; (8) Cys-Pro-Leu-Val-Ser-Leu-Arg-Asp-His-Ser-Cys; (9) Cys-Lys-Gln-Ser-Tyr-Leu-His-His-Leu-Leu-Cys; (10) Cys-Phe-Gln-Pro-Leu-Thr-Pro-Leu-Cys-Arg-Cys; and (11) Cys-Gln-Ser-Tyr-His-Glu-Leu-Leu-Leu-Gln-Cys. An independent claim is also included for an expression vector, functional in mammalian cells, that contains a DNA sequence encoding (A). ACTIVITY : Cytostatic. H-125 non-small cell lung carcinoma cells were implanted in mice together with 10 mg/kg of peptide (1) Cys-Ser-Val-Arg-Gln-Gly-Pro-Val-Gln-Lys-Cys and the same dose of peptide administered every other day. After 30 days, the tumor volume was about 0.6 mm 3 compared with 1.5 mm 3 for untreated controls. MECHANISM OF ACTION : (A) inhibit casein kinase II and also bind to the phosphorylation site at positions 28-38 in the E7 oncoprotein of HPV, so are toxic to cervical carcinoma cells and also increase the sensitivity of such cells to interferon; Gene therapy.