Abstract: The present invention relates to pharmaceutical compositions and methods for the treatment of carcinomas and sarcomas. In particular, the invention provides a pharmaceutical composition comprising a peptide or pharmaceutically acceptable salt thereof for use in treating a carcinoma or a sarcoma in a human subject, wherein the peptide comprises an amino acid sequence as set forth in SEQ ID NO: 1 and a cell penetrating peptide and wherein the pharmaceutical composition is systemically administered to the subject weekly to provide a dose of the peptide of about 15-65 mg/m2 body surface area (BSA) per week, calculated as the free form of the peptide.

Abstract: The present invention provides an agent, or a composition containing an agent, for use in treating or preventing a bacterial infection in a subject, 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 X1X2X3X4X5 (SEQ ID NO: 1) and wherein: X1 is a basic amino acid; X2 is an aromatic amino acid; X3 is an uncharged amino acid other than an aromatic amino acid, Glycine (G) and Proline (P); X4 is any amino acid other than Proline (P), an acidic amino acid or an aromatic amino acid; and X5 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 compositions of the invention may be used as single agents.

Abstract: 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 the 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 X1X2X3X4X5 (SEQ ID NO: 1) and wherein: X1 is a basic amino acid; X2 is an aromatic amino acid; X3 is an uncharged amino acid other than an aromatic amino acid, Glycine (G) and Proline (P); X4 is any amino acid other than Proline (P), an acidic amino acid or an aromatic amino acid; and X5 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 compositions of the invention may be used as single agents.

Abstract: 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 X1X2X3X4X5 (SEQ ID NO: 1) and wherein: X1 is a basic amino acid; X2 is an aromatic amino acid; X3 is an uncharged amino acid other than an aromatic amino acid, Glycine (G) and Proline (P); X4 is any amino acid other than Proline (P), an acidic amino acid or an aromatic amino acid; and X5 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 compositions of the invention may be used as single agents.

Abstract: The present invention provides an agent, or a composition containing an agent, for use in treating or preventing a bacterial infection in a subject, 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 X1X2X3X4X5 (SEQ ID NO: 1) and wherein: X1 is a basic amino acid; X2 is an aromatic amino acid; X3 is an uncharged amino acid other than an aromatic amino acid, Glycine (G) and Proline (P); X4 is any amino acid other than Proline (P), an acidic amino acid or an aromatic amino acid; and X5 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 compositions of the invention may be used as single agents.

Abstract: The present invention provides an agent, or a composition containing an agent, for use in treating or preventing a bacterial infection in a subject, 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

Abstract: 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 the 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 X1X2X3X4X5 (SEQ ID NO: 1) and wherein: X1 is a basic amino acid; X2 is an aromatic amino acid; X3 is an uncharged amino acid other than an aromatic amino acid, Glycine (G) and Proline (P); X4 is any amino acid other than Proline (P), an acidic amino acid or an aromatic amino acid; and X5 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 compositions of the invention may be used as single agents.

Abstract: The present invention provides an agent, or a composition containing an agent, for use in treating or preventing a bacterial infection in a subject, 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 X1X2X3X4X5 (SEQ ID NO: 1) and wherein: X1 is a basic amino acid; X2 is an aromatic amino acid; X3 is an uncharged amino acid other than an aromatic amino acid, Glycine (G) and Proline (P); X4 is any amino acid other than Proline (P), an acidic amino acid or an aromatic amino acid; and X5 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 compositions of the invention may be used as single agents.

Abstract: Disclosed is A method of treatment of a disorder or condition where it is desirable to inhibit the growth of cells, or a method of treatment which involves cytostatic therapy by administering an oligopeptidic compound to a subject in need thereof. The oligopeptidic compound is capable of interacting with proliferating cell nuclear antigen (PCNA) The compound comprises a PCNA interacting motif which is: which is: [K/R]-[F/Y/W]-[L/I/V/A/M]-[L/I/V/A/M]-[K/R] (SEQ ID NO. 28). The oligopeptidic compound has 9-70 subunits and at least one signal sequence. The signal sequence is a nuclear localization signal sequence and/or a cell penetrating signal sequence. In the compound a PCNA interacting motif is N-terminal to a signal sequence.

Abstract: The present invention provides an agent, or a composition containing an agent, for use in treating or preventing a bacterial infection in a subject, 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 add, preferably a basic amino add 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

Abstract: Disclosed is A method of treatment of a disorder or condition where it is desirable to inhibit the growth of cells, or a method of treatment which involves cytostatic therapy by administering an oligopeptidic compound to a subject in need thereof. The oligopeptidic compound is capable of interacting with proliferating cell nuclear antigen (PCNA) The compound comprises a PCNA interacting motif which is: which is: [K/R]-[F/Y/W]-[L/I/V/A/M]-[L/I/V/A/M]-[K/R] (SEQ ID NO. 28). The oligopeptidic compound has 9-70 subunits and at least one signal sequence. The signal sequence is a nuclear localization signal sequence and/or a cell penetrating signal sequence. In the compound a PCNA interacting motif is N-terminal to a signal sequence.

Abstract: Disclosed is an oligopeptidic compound capable of interacting with proliferating cell nuclear antigen (PCNA), wherein the compound comprises a PCNA interacting motif which is: (SEQ?ID?NO.?28) [K/R]-[F/Y/W]-[L/I/V/A/M]-[L/I/V/A/M]-[K/R]; wherein the oligopeptidic compound has 9-70 subunits and comprises at least one signal sequence, wherein the signal sequence is a nuclear localization signal sequence and/or a cell penetrating signal sequence and wherein in said compound a PCNA interacting motif is N-terminal to a signal sequence. Also disclosed are methods of treatment of a disorder or condition where it is desirable to inhibit the growth of cells, or a method of treatment which involves cytostatic therapy, or a method of treatment of inflammation said method comprising administering the oligopeptidic compound to a subject in need thereof.

Abstract: The present invention provides an agent, or a composition containing an agent, for use in treating or preventing a bacterial infection in a subject, 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 X1X2X3X4X5 (SEQ ID NO: 1) and wherein: X1 is a basic amino acid; X2 is an aromatic amino acid; X3 is an uncharged amino acid other than an aromatic amino acid, Glycine (G) and Proline (P); X4 is any amino acid other than Proline (P), an acidic amino acid or an aromatic amino acid; and X5 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 compositions of the invention may be used as single agents.

Abstract: 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 X1X2X3X4X5 (SEQ ID NO: 1) and wherein: X1 is a basic amino acid; X2 is an aromatic amino acid; X3 is an uncharged amino acid other than an aromatic amino acid, Glycine (G) and Proline (P); X4 is any amino acid other than Proline (P), an acidic amino acid or an aromatic amino acid; and X5 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 compositions of the invention may be used as single agents.

Abstract: Disclosed is an oligopeptidic compound capable of interacting with proliferating cell nuclear antigen (PCNA), wherein the compound comprises a PCNA interacting motif which is: (SEQ?ID?NO.?28) [K/R]-[F/Y/W]-[L/I/V/A/M]-[L/I/V/A/M]-[K/R]; wherein the oligopeptidic compound has 9-70 subunits and comprises at least one signal sequence, wherein the signal sequence is a nuclear localization signal sequence and/or a cell penetrating signal sequence and wherein in said compound a PCNA interacting motif is N-terminal to a signal sequence. Also disclosed are methods of treatment of a disorder or condition where it is desirable to inhibit the growth of cells, or a method of treatment which involves cytostatic therapy, or a method of treatment of inflammation said method comprising administering the oligopeptidic compound to a subject in need thereof.

Abstract: The present invention provides an oligopeptidic compound comprising a PCNA interacting motif, or a nucleic acid molecule comprising a sequence encoding said oligopeptidic compound, for use in therapy, wherein the PCNA interacting motif is X1X2X3X3?X1?- (SEQ ID NO: 1), wherein X1 and X1?- are independently selected from the group of basic amino acids, X2 is a lipophilic amino acid and X3 and X3? are independently selected from the group of uncharged amino acids; and wherein the oligopeptidic compound is further characterized by at least one of the following: (i) the oligopeptidic compound comprises at least one signal sequence; (ii) the PCNA interacting motif is [K/R]-F-[L/I/V]-[L/I/V]-[K/R] (SEQ ID NO: 27). Particularly the therapy may be the treatment of a disorder or condition where it is desirable to inhibit the growth of cells, for example a hyperproliferative disorder, or a treatment which involves cytostatic therapy e.g., myeloablation.

Abstract: The present invention provides an oligopeptidic compound comprising a PCNA interacting motif, or a nucleic acid molecule comprising a sequence encoding said oligopeptidic compound, for use in therapy, wherein the PCNA interacting motif is X1X2X3X3?X1?? (SEQ ED NO: 1), wherein X1 and X1?? are independently selected from the group of basic amino acids, X2 is a lipophilic amino acid and X3 and X3? are independently selected from the group of uncharged amino acids; and wherein the oligopeptidic compound is further characterised by at least one of the following: (i) the oligopeptidic compound comprises at least one signal sequence; (ii) the PCNA interacting motif is [K/R]-F-{LIV]-[LIV]-[K/R] (SEQ ID NO. 27). Particularly the therapy may be the treatment of a disorder or condition where it is desirable to inhibit the growth of cells, for example a hyperproliferative disorder, or a treatment which involves cytostatic therapy e.g. myeloablation.

Abstract: Cells such as mammalian or genetically modified cells are encapsulated in high-G alginate that provokes reduced immune response during transplantation or implantation. The alginate contains greater than 50% .alpha.-L-guluronic acid and a minimal amount of mannuronic acid. The amount of .alpha.-L-guluronic acid is preferably at least 65% and more preferably at least 85%. Encapsulation is carried out by suspending cells in a solution of the high-G alginate, forming drops of the solution and contacting the drops with calcium ions to gel the alginate and form microcapsules containing the cells. The microcapsules may contain multiple layers with the high-G alginate preferably forming the outermost layer.

Abstract: The present invention is directed to a material and method for the stimulation of the production of cytokines. Several polysaccharides, including polymers of different size of .sym.1-4 linked D-mannuronic acid (poly-M and M-blocks), chitosan and cellulose oxidized in C-6 position C60XY) induce human monocytes to produce the cytokines. Preferably, the molecular weights of poly-M and chitosan are above 50,000 and 20,000 respectively. Pretreatment of the monocytes with IFN-.gamma. increases the cytokine production from monocytes stimulated with all polysaccharides tested. The subject polysaccharides worked in vivo and in vitro.The present invention has therapeutic utility as vaccine adjuvants and components. Therapeutic compositions comprising biologically active quantities of the compositions of the present invention may be employed to potentiate antibody production in response to vaccine antigens. Anti-tumor, anti-bacteriological, anti-fungal and anti-viral effects may be expected.

Abstract: A family of compounds effective in inhibiting interleukin-1 (IL-1) production, interleukin-6 (IL-6), tumor necrosis factor (TNF) production, and the production of other leukocyte derived cytokines is comprised of oligomers and polymers of .alpha.1-4 linked L-guluronic acid residues which may be administered to a human or mammal in an amount sufficient to inhibit the production effect of leukocyte-derived cytokines. The inhibition of IL-1, IL-6 and TNF, and other cytokines in mammals is implicated in alleviation of a wide variety of disease conditions.