Lysosomal targeting of immunogens

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai

Patent

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

4241851, 4241921, 435 693, 4352523, 4353201, 530350, 530395, 530806, 536 234, 536 235, A61K 3170, C12N 1562

Patent

active

056332343

ABSTRACT:
The inventors have discovered a targeting signal that will direct proteins to the endosomal/lysosomal compartment, and they have demonstrated that chimeric proteins containing a luminal antigenic domain and a cytoplasmic endosomal/lysosomal targeting signal will effectively target antigens to that compartment, where the antigenic domain is processed and peptides from it are presented on the cell surface in association with major histocompatibility (MHC) class II molecules. Chimeric DNA encoding the antigen of interest, linked to an endosomal/lysosomal targeting sequence, inserted in an immunization vector, can introduce the chimeric genes into cells, where the recombinant antigens are expressed and targeted to the endosomal/lysosomal compartment. As a result, the antigens associate more efficiently with MHC class II molecules, providing enhanced in vivo stimulation of CD4.sup.+ T cells specific for the recombinant antigen. Delivering antigens to an endosomal/lysosomal compartment by means of chimeric constructs containing such lysosomal targeting signals will be of value in any vaccination or immunization strategy that seeks to stimulate CD4.sup.+ MHC class II restricted immune responses.

REFERENCES:
patent: 4400376 (1983-08-01), Sanderson
patent: 4406885 (1983-09-01), Pinter
patent: 4446128 (1984-05-01), Baschang et al.
patent: 4448765 (1984-05-01), Ash et al.
patent: 4454116 (1984-06-01), Brinton
patent: 4578458 (1986-03-01), Pier
patent: 4593002 (1986-06-01), Dulbecco
patent: 4681762 (1987-07-01), Oeschger et al.
patent: 4738846 (1988-04-01), Rose et al.
patent: 4769330 (1988-09-01), Paoletti
patent: 4920209 (1990-04-01), Davis et al.
Paul, W.E. Fundamental Immunology 2nd Edition see pp, 188-190 and 936 1989.
Tizard, I. An Introduction to Veterinary Immunology see p. 253 1982.
Inaba et al. J. Exp. Med. 172:631-640 Aug. 1990.
Scheicher et al. J. Immunol. Methods 154:253-264 1992.
Peters, et al., "Targeting of a Lysosomal Membrane Protein: A Tyrosine-Containing Endocytosis Signal in the Cytoplasmic Tail of Lysosomal Acid Phosphatase is Necessary and Sufficient for Targeting to Lysosomes," EMBO Journal, 9:3497-3506 (1990).
Harding, et al., "Liposome-Encapsulated Antigens Are Processed in Lysosomes, Recycled , and Presented to T Cells," Cell, 64:393-401 (1991).
Sanger, et al., "DNA Sequencing With Chain-Terminating Inhibitors," Proc. Nat. Acad. Sci. U.S.A., 74:5463-5467 (1977).
Hughes, et al., "Murine Fibroblast Plasma Membrane Proteins Identified by Monoclonal Antibodies. In: Leukaemias, Lymphomas and Papillomas: Comparative Aspects," pp. 65-86 (1980) P. A. Bachmann (ed.). Taylor and Francis Ltd., London.
Hughes, et al., "Characterization of Plasma Membrane Proteins Identified by Monoclonal Antibodies," J. Biol. Chem., 256:664-671 (1981).
Mengod, et al., "Murine Cell Surface Glycoproteins: Immunochemical Analysis of a Major Differentiation Alloantigen of Phagocytotic Cells," Arch. Biochem. Biophys., 209:718-722 (1981).
Hughes, et al., "Murine Cell Surface Glycoproteins: Identification, Purification, and Characterization of a Major Glycosylated Component of 110,000 Daltons by Use of a Monoclonal Antibody," J. Biol. Chem., 257:3970-3977 (1982).
Hughes, et al., "Murine Cell Surface Glycoproteins: Purification of the Polymorphic Pgp-1 Antigen and Analysis of its Expression on Macrophages and Other Myeloid Cells," J. Biol. Chem., 258:1014-1021 (1983).
Chen, et al., "Lysosome-Associated Membrane Proteins: Characterization of LAMP-1 of Macrophage P388 and Mouse Embryo 3T3 Cultured Cells," Arch Biochem. Biophys., 239:574-586 (1985).
Chen, et al., "Identification of Two Lysosomal Membrane Glycoproteins," J. Cell Biol., 101:85-95 (1985).
Lewis, et al., "Glycoproteins of the Lysosomal Membrane," J. Cell Biol., 100:1839-1847 (1985).
Taylor, et al., "The Use of Phosphorothioate-Modified DNA in Restriction Enzyme Reactions to Prepare Nicked DNA" Nucl. Acids Res., 13:8749-8764 (1985).
Taylor, et al., "The Rapid Generation of Oligonucleotide-Directed Mutations at a High Frequency Using Phosphorothioate-Modified DNA," Nucl. Acids Res., 13:8765-8785 (1985).
Chen, et al., "Lysosomal Membrane Glycoproteins: Properties of LAMP-1 and LAMP-2," Biochem. Soc. Symp., 51:97-112 (1986).
Lippincott-Schwartz, et al., "Lysosomal Membrane Dynamics: Structure And Interorganellar Movement of a Major Lysosomal Membrane Glycoprotein," J. Cell Biol., 102:1593-1605 (1986).
Barriocanal, et al., "Biosynthesis, Glycosylation, Movement Through the Golgi System, and Transport To Lysosomes By an N-Linked Carbohydrate-Independent Mechanism of Three Lysosomal Integral Membrane Proteins," J. Biol. Chem., 261:16755-16763 (1986).
Nakamaye, et al., "Inhibition of Restriction Endonuclease Nci I Cleavage by Phosphorothioate Groups and its Application to Oligonucleotide-Directed Mutagenesis," Nucl. Acids Res., 14:9679-9698 (1986).
D'Souza, et al., "A Kinetic Analysis of Biosynthesis and Localization of a Lysosome-Associated Membrane Glycoprotein," Arch. Biochem. Biophys., 249:522-532 (1986).
Lippincott-Schwartz, et al., "Cycling of the Integral Membrane Glycoprotein, LEP100, Between Plasma Membrane and Lysosomes: Kinetic and Morphological Analysis," Cell, 49:669-677 (1987).
Green, et al., "Kinetics of Intracellular Transport and Sorting of Lysosomal Membrane and Plasma Membrane Proteins," J. Cell Biol., 105:1227-1240 (1987).
Fambrough, et al., "Structure of LEP100, a Glycoprotein that Shuttles Between Lysosomes and the Plasma Membrane, Deduced from the Nucleotide Sequence of the Encoding cDNA," J. Cell. Biol., 106:61-67 (1988).
Sayers, et al., "5'-3' Exonucleases in Phosphorothioate-Based Oligonucleotide-Directed Mutagenesis," Nucl. Acids Res., 16:791-802 (1988).
Goldenthal, et al., "Pre-lysosomal Divergence of Alpha.sub.2 -Macroglobulin and Transferrin: A Kinetic Study Using a Monoclonal Antibody Against a Lysosomal Membrane Glycoprotein (LAMP-1)," J. Histochem. and Cytochem., 36:391-400 (1988).
Hotta, H., et al., "Molecular Cloning and Characterization of An Antigen Associated with Early Stages of Melanoma Tumor Progression," Cancer Res., 48:2955-2962 (1988).
Chen, et al., "Isolation and Sequencing of a cDNA Clone Encoding Lysosomal Membrane Glycoprotein Mouse LAMP-1: Sequence Similarity to Proteins Bearing Onco-Differentiation Antigens," J. Biol. Chem., 263:8754-8758 (1988).
Carlsson, et al., "Isolation and Characterization of Human Lysosomal Membrane Glycoproteins, h-LAMP-1 and h-LAMP-2: Major Sialoglycoproteins Carrying Polylactosaminoglycan," J. Biol. Chem., 263:18911-18919 (1988).
Fukuda, et al., "Cloning of cDNAs Encoding Human Lysosomal Membrane Glycoproteins, h-LAMP-1 and h-LAMP-2: Comparison of Their Deduced Amino Acid Sequences," J. Biol. Chem., 263:18920-18928 (1988).
Arterburn, et al., "Biosynthesis and Processing of Lysosomal Membrane Glycoproteins," In: Intracellular Trafficking of Proteins, pp. 472-503 (1989) (C.J. Steer and J.A. Hanover, Eds.) Cambridge University Press, England.
Sandoval, et al., "Lysosomal Integral Membrane Glycoproteins are Expressed at High Levels in the Inclusion Bodies of I-Cell Disease Fibroblasts," Arch. Biochem. Biophys., 271:1-11 (1989).
Kornfield, et al., "The Biogenesis of Lysosomes," Annu. Rev. Cell Biol., 5:483-525 (1989).
Gottschalk, et al., "Sequential Processing of Lysosomal Acid Phosphatase by a Cytoplasmic Thiol Proteinase and a Lysosomal Aspartyl Proteinase," EMBO J., 8:3215-3219 (1989).
Wolffe, et al., "The cDNA Sequence of Mouse Pgp-1 and Homology to Human CD44 Cell Surface Antigen and Proteoglycan Core/Link Proteins," J. Biol. Chem., 265:341-347 (1990).
Chen, et al., "NPXY, A Sequence Often Found in Cytoplasmic Tails, is Required for Coated Pit-Mediated Internalization of the Low Density Lipoprotein Receptor," J. Biol. Chem., 265:3116-3123 (1990).
Cha, et al., "The cDNA Sequence of Mouse LAMP-2," J. Biol. Chem.,265:5008-5013 (1990).
Arterburn, et al., "The Disulfide Structure of Mouse Lysosome-Associated Membrane Protein 1," J. Biol. Chem., 265:7419-7423 (1990).
Metzelaar, et al., "CD63 Antigen: A Novel Lysosomal Membrane Glycoprotein, Cloned By a Screening Procedure for

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

Lysosomal targeting of immunogens does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Lysosomal targeting of immunogens, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Lysosomal targeting of immunogens will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-2329096

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.