| 摘要 |
The present invention provides an agent, or composition containing an agent, for use in treating or preventing hypercytokinemia in a subject resulting from cytokine release from non-proliferating immune cells in blood, wherein said agent comprises: (i) an oligopeptidic compound comprising a PCNA interacting motif and a domain that facilitates the cellular uptake of said compound, wherein the PCNA interacting motif is X1X2X3X4X5X6 (SEQ ID NO: 1 ) and wherein: X1 is a basic amino acid; X2 is an aromatic amino acid; X3 is an aromatic amino acid or a hydrophobic amino acid that has an R group comprising at least three carbon atoms; X4 is an uncharged amino acid other than an aromatic amino acid, Glycine (G) and Proline (P); X5 is any amino acid other than an acidic amino acid or an aromatic amino acid; and X6 is any amino acid other than an acidic amino acid or an aromatic amino acid, preferably a basic amino acid or Proline (P), wherein when X3 is not an aromatic amino acid, X5 is not lysine (K) and X6 is a basic amino acid or Proline (P); or (ii) a nucleic acid molecule comprising a sequence encoding the oligopeptidic compound of (i). In certain aspects the agent and composition of the invention may be used as single agents. In other aspects of the invention the agents and composition may be used in conjunction with one or more additional active agents, such as kinase inhibitors. |
