Infective protein delivery system
AssigneeChiron Corporation
InventorsMichael Kriegler, Carl F. Perez
Life of this patent
Estimating the term…
Abstract
A virion expression system for a desired protein packaged in an envelope derived from a retrovirus useful in administering proteins which cross cell membranes in order to serve their function. Preferred virions are those that carry an RNA sequence that encodes cytokines or lymphokines, and includes IL-2, multiple drug resistance protein, and TNF.
Claims19
A cultured and transformed ex vivo human lymphocyte which expresses a protein cytotoxic to a target tumor cell, said protein is a human protein not normally expressed in said lymphocyte, the ex vivo human lymphocyte having integrated in DNA therein a proviral DNA sequence from a replication defective retroviral vector, said proviral DNA sequence comprising a gene heterologous to the provirus and encoding the protein, said gene operably linked to a promoter for expression of said protein in said lymphocyte, and which gene is expressed by said ex vivo transformed lymphocyte to produce amounts of said protein which are cytotoxic to said target tumor cells, wherein said protein is prohormone TNF lacking the first twelve amino acids of mature hormone TNF ("TNF.increment.(1.fwdarw.12)") or prohormone TNF lacking the first and twelfth amino acids of mature hormone TNF ("TNF.increment.(1+12") or a .gamma. interferon signal peptide-mature TNF fusion protein (TNF .gamma. sig).
A cultured and transformed transformed ex vivo human TIL cell which expresses a protein cytotoxic to a target tumor cell, the cultured and transformed ex vivo human TIL cell having genomic DNA therein, said genomic DNA having integrated therein a proviral DNA sequence from a replication defective retroviral vector, said proviral DNA sequence comprising a gene heterologous to the provirus and encoding the protein, said gene operably linked to a promoter for expression of said protein in said TIL cell, and which gene is expressed by said ex vivo transformed lymphocyte to produce amounts of said protein which are cytotoxic to said target tumor cells, wherein said protein is prohormone TNF lacking the first twelve amino acids of mature hormone TNF ("TNF.increment.(1.fwdarw.12)") or prohormone TNF lacking the first and twelfth amino acids of mature hormone TNF ("TNF.increment.(1+12)") or a .gamma. interferon signal peptide-mature TNF fusion protein (TNF .gamma. sig).
A composition comprising:
- a) a cultured and transformed ex vivo human lymphocyte which expresses a protein cytotoxic to a target tumor cell, said protein is a human protein not normally expressed in said lymphocyte, the cultured and transformed ex vivo human lymphocyte having integrated in DNA therein a proviral DNA sequence from a replication defective retroviral vector, said proviral DNA sequence comprising a gene heterologous to the provirus and encoding the recombinant protein, said gene operably linked to a promoter for expression of said protein in said lymphocyte, and which gene is expressed by said ex vivo transformed lymphocyte to produce amounts of said protein which are cytotoxic to said target tumor cells, wherein said protein is prohormone TNF lacking the first twelve amino acids of mature hormone TNF ("TNF.increment.(1.fwdarw.12)") or prohormone TNF lacking the first and twelfth amino acids of mature hormone TNF ("TNF.increment.(1+12)") or a .gamma. interferon signal peptide-mature TNF fusion protein (TNF .gamma. sig);
- and
- b) an excipient.
A composition comprising:
- a) a cultured and transformed ex vivo human TL cell which expresses a protein cytotoxic to a target tumor cell, said protein is a human protein not normally expressed in said TIL cell, the transformed ex vivo human TIL cell comprising an ex vivo human TIL cell having genomic DNA therein, said genomic DNA having integrated herein a proviral DNA sequence from a replication defective retroviral vector, said proviral DNA sequence comprising a gene heterologous to the provirus and encoding the protein, said gene operably linked to a promoter for expression of said protein in said TIL cell, and which gene is expressed by said ex vivo transformed lymphocyte to produce amounts of said protein which are cytotoxic to said target tumor cells, wherein said protein is prohormone TNF lacking the first twelve amino acids of mature hormone TNF ("TNF.increment.(1.fwdarw.12)") or prohormone TNF lacking the first and twelfth amino acids of mature hormone TNF ("TNF.increment.(1+12)") or a .gamma. interferon signal peptide-mature TNF fusion protein (TNF .gamma. sig);
- and
- b) an excipient.
Dependencies are inferred from the claim text.