Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1995-06-06
1999-06-08
Campell, Bruce R.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
A61K 4800
Patent
active
059104864
ABSTRACT:
Methods and compositions for modulating protein function in a cell involving intracellular expression of an antibody homologue that binds to the protein within the cell are disclosed. In a preferred embodiment, an antibody homologue, such as a single chain Fv (sFv) fragment, is expressed within an intracellular compartment of a cell, such as the endoplasmic reticulum (ER), to inhibit cell surface expression of a membrane protein. Preferably, the cell is a malignant mammalian cell and the protein is a cell surface receptor oncoprotein, such as c-erbB2. Intracellular binding of the antibody homologue to the receptor oncoprotein inhibits its surface expression and, moreover, inhibits cell proliferation and cell survival. Isolated nucleic acid molecules encoding anti-c-erbB2 antibody homologues, as well as recombinant expression vectors and host cells incorporating these nucleic acid molecules, are also disclosed.
REFERENCES:
Adams, G.P. et al., "Highly Specific in Vivo Tumor Targeting by Monovalent and Divalent Forms of 741F8 Anti-c-erbB-2 Single Chain Fv" Cancer Research, vol. 53, pp. 4026-4034, Sep. 1, 1993.
Batra, J.K. et al., "Recombinant anti-erbB2 immunotoxins containing Pseudomonas exotoxin" Proc. Natl. Acad. Sci. USA, vol. 89, pp. 5867-5871, Jul. 1992.
Biocca, S. et al., "Intracellular Expression of Anti-p21.sup.ras Single chain Fv Fragments Inhibits Meiotic Maturation of Xenopus Oocytes" Biochemical and Biophysical Research Communications, vol. 197, No. 2, pp. 422-427, Dec. 15, 1993.
Biocca, S. et al., "Intracellular Immunization with Cytosolic Recombinant Antibodies" Bio/Technology, vol. 12, pp. 396-399, Apr. 1994.
Carlson, J.R., "A New Means of Inducibly Inactivating a Cellular Protein" Molecular and Cellular Biology, vol. 8, No. 6, pp. 2638-2646, Jun. 1988.
Carter, P., et al., "Humanization of an anti-p185.sup.HER2 antibody for human cancer therapy" Proc. Natl. Acad. Sci. USA, vol. 89, pp. 4285-4289, May 1992.
DeSantes, K. et al., "Radiolabeled Antibody Targeting of the HER-2
eu Oncoprotein" Cancer Research, vol. 52, pp. 1916-1923, Apr. 1, 1992.
Drebin, J.A. et al., "Monoclonal antibodies specific for the neu oncogene product directly mediate anti-tumor effects in vivo" Oncogene, vol. 2, pp. 387-394, 1988.
Fendly, B.M. et al., "Characterization of Murine Monoclonal Antibodies Reactive of Either the Human Epidermal Growth Factor Receptor or HER2
eu Gene Product" Cancer Research, vol. 50, pp. 1550-1558, Mar. 1, 1990.
Hiatt, A. et al., "Production of antibodies in trangenic plants" Nature, vol. 342, pp. 76-78, Nov. 2, 1989.
Hudziak, R.M. et al., "Increased expression of the putative growth factor receptor p185.sup.HER2 causes transformation and tumorigenesis of NIH 3T3 cells" Proc. Natl. Acad. Sci. USA, vol. 84, pp. 7159-7163, Oct. 1987.
Marasco, W.A. et al., "Design, intracellular expression, and activity of a human anti-human immunodeficiency virus type 1 gp120 single-chain antibody" Proc. Natl. Acad. Sci. USA, vol. 90, pp. 7889-7893, Aug. 1993.
Moritz, D. et al, "Cytotoxic T lymphocytes with a grafted recognition specificity for ERBB2-expressing tumor cells" Proc. Natl. Acad. Sci. USA, vol. 91, pp. 4318-4322, May 1994.
Muller, W.J. et al., "Single-Step Induction of Mammary Adenocarcinoma in Transgenic Mice Bearing the Activated c-neu Oncogene" Cell, vol 54, pp. 105-115, Jul. 1, 1988.
Stancovski, I. et al, "Targeting of T Lymphocyts to Neu/HER2-Expressing Cells Using Chimeric Single Chain Fv Receptors" Journal of Immunology, vol. 151, No. 11, pp. 6577-6582, Dec. 1, 1993.
Wels W. et al., "Construction, Bacterial Expression and Characterization of a Bifunctional Single-Chain Antibody-Phosphatase Fusion Protein Targeted to the Human ERBB2-Receptor" Biotechnology, vol. 10, pp. 1128-1132, 1992.
Wels, W. et al., "Diminution of Antibodies Directed Against Tumor Cell Surface Epitopes: A Single Chain Fv Fusion Molecule Specifically Recognized the Extracellular Domain of the c-erb B-2 Receptor" J. Steroid Biochem. Molec. Biol., vol. 43, No. 1-3, pp. 1-7, 1992.
Wels, W. et al., "Selective Inhibition of Tumor Cell Growth by a Recombinant Single-Chain Antibody-Toxin Specific for the erbB-2 Receptor" Cancer Research, vol. 52, pp. 6310-6317, Nov. 15, 1992.
Werge, T.M. et al., "Intracellular immunization: Cloning and intracellular expression of a monoclonal antibody to the p21.sup.ras "FEBS, vol. 274, No. 1,2, pp. 193-198, Nov. 1990.
Winter, G. and C. Milstein, "Man-made antibodies" Nature, vol. 349, pp. 293-299, Jan. 24, 1991.
Brocea et al BBRC 197(2) 422, 1993, Jun. 1997.
Orkin et al. Dec. 1995, Jun. 1997.
Caufen et al New Scientist, Nov. 25, 1995, Jun. 1997.
Marshal et al Science 269:1050, 1995, Jun. 1997.
Werge et al FEBS 274 (1,2): 193, 1990, Jun. 7, 1997.
Wels et al Cancer Res. 52: 6310, 1992, Jun. 7, 1997.
Marasco et al PNAS 90: 7889, 1993, Jun. 7, 1997.
Wels et al J. Steroid Biochem Mol. Biol 43(1-3): Jan. 1992, Jun. 7, 1997.
J Deshane et al. (1994) Gene Therapy 1: 332-337.
IM Harwerth et al (1993) British J Cancer 68: 1140-1145.
JA Drebin et al (1986) Proc Natl Acad SCi USA 83: 9129-9133.
JG Altin et al (1991) Growth Factors 4: 145-155 (Abstract only).
JR Starkey et al. (1991) FASEB J 5: A1259.
R Hesketh (1995) The Oncogene Facts Book pp. 32-42.
Curiel David T.
Deshane Jessy
Adler Benjamin Aaron
Campell Bruce R.
UAB Research Foundation
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