DNA corresponding to a peptide from antigen MUC-1 for triggering an immune response to tumor cells

摘要

Peptide (I) derived from the MUC-1 gene and able to induce an HLA (human leukocyte antigen)-A2-restricted immune reaction against tumor cells, is new. (I) has a 10 amino acid sequence (S1) fully defined in the specification, a sequence derived from the MUC-1 signal peptide, especially a 9 amino acid sequence (S2) fully defined in the specification, and/or modified forms of both. (I) has the formula (S1) and/or (S2). Ser-Thr-Thr-Ala-Pro-Pro-Val-His-Asn-Val (S1) Leu-Leu-Leu-Leu-Thr-Val-Leu-Thr-Leu (S2) Independent claims are also included for the following: (1) a nucleic acid (II) comprising a sequence that encodes (I); and (2) a pharmaceutical composition containing (I) and/or (II) in an amount sufficient to induce an MHC (major histocompatibility complex)-1 restricted immune response. ACTIVITY : Antitumor. MECHANISM OF ACTION : Induction of cytotoxic T cells that are antigen-specific and have HLA-A2-restricted activity against MUC-1-expressing tumor cells. Dendritic cells were incubated with (I) in presence of autologous peripheral blood mononuclear cells to induce cytotoxic T cells. These were then tested for lytic ability against tumor cells and were able to lyze those that expressed both HLA-A2 and MUC-1 (e.g. MCF-7 breast cancer cells) but were not active against cells that lacked expression of either HLA-A2 or MUC-1.