Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Reexamination Certificate
1999-03-25
2002-09-24
Jones, Dwayne C. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
C530S350000, C530S827000, C424S193100, C424S184100
Reexamination Certificate
active
06455493
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates generally to treating diseases with immunotoxins.
2. Description of the Prior Art
In the field of treating diseases with immunotoxins, an ongoing problem has been to insure that the immunotoxins kill target cells and only target cells. As described in Frankel et al., “Meeting Report: Advances in Immunotoxin Biology and Therapy: A Summary of the Fourth International Symposium on Immunotoxins” in
Cancer Research
56 (Feb. 15, 1996), pp. 926-932, in the case of immunotoxin treatments for cancer there are few treatments which can deliver an effective amount of a toxin to a cell and, and the toxicities which result from the treatments have generally been less than those for conventional chemotherapy.
SUMMARY OF THE INVENTION
In one aspect, the present invention provides a heat shock protein immunotoxin comprising: at least a fragment of a heat shock protein, the fragment being capable of being bound by an immune cell; and a toxin bound to the fragment.
In a second aspect, the present invention provides a method for reducing the number of at least one type of immune cells in an individual comprising the step of administering a heat shock protein immunotoxin to an individual in an amount sufficient to decrease the number of immune cells of at least one type in the individual, the heat shock protein immunotoxin comprising at least a fragment of a heat shock protein, the fragment being capable of being bound by an immune cell; and a toxin bound to the fragment.
In a third aspect, the present invention provides a method for reducing the number of at least one type of immune cells in an organ comprising the step of administering a heat shock protein immunotoxin to at least a portion of an organ in an amount sufficient to decrease the number of immune cells of at least one type in the organ, the heat shock protein immunotoxin comprising at least a fragment of a heat shock protein, the fragment being capable of being bound by an immune cell; and a toxin bound to the fragment.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Definitions
For the purposes of the present invention, the term “toxin” refers to any chemical or substance which kills cells, renders them inactive or causes them to be unable to perform their normal functions. Examples of such toxins include ricin, saporin, Shiga toxin,
Pseudomonas exotoxin
, radioactive isotopes (either alone or as part of a molecule), etc. Toxins suitable for use with the present invention may also include chemotherapeutic agents such as: bleomycin, methotrexate, cyclophosphamide, vinca alkaloids, adriamycin, cisplatin, etoposides, etc.
For the purposes of the present invention, the term “heat shock protein immunotoxin” refers to heat shock protein-peptide complexes where the peptide is a toxin, immunotoxins in which a heat shock protein or a fragment of a heat shock protein is covalently bound to a toxin, and immunotoxins in which a heat shock protein or a fragment of a heat shock protein is combined with a toxin comprising a protein oligonucleotide sequence or molecule.
For the purposes of the present invention, the terms “bind” and “binding” refer to both covalent and non-covalent binding.
For the purpose of the present invention, the term “fragment” can refer to a portion of a heat shock protein or an entire heat shock protein.
For the purposes of the present invention, the term “oligonucleotide” refers to any oligonucleotide, including double and single-stranded DNA, RNA, PNAs (peptide nucleic acids) and any sequence of nucleic acids, either natural or synthetic, derivatized or underivatized.
For the purposes of the present invention the term “peptide” refers to all types of peptides and conjugated peptides including: peptides, proteins, polypeptides, protein sequences, amino acid sequences, denatured proteins, antigens, oncogenes and portions of oncogenes.
For the purposes of the present invention the term “individual” refers to either an individual person or animal from whom a cell lysate, heat shock protein, or peptide is obtained or an individual patient who is treated according to a method of the present invention.
For the purposes of the present invention, the term “immune cells” refers to B lymphocytes, T lymphocytes, antigen presenting cells, macrophages, monocytes, natural killer cells, and dendritic cells.
For the purposes of the present invention, the term “antigen presenting cells” refers to B lymphocytes, macrophages, and dendritic cells.
For the purposes of the present invention, the term “organ” is used in the broad sense of this term to include such organs as the skin, bone marrow, etc.
Description
The present invention provides a method for specifically destroying or inhibiting cellular function of immune cells which bind heat shock proteins or portions of heat shock proteins.
Heat shock proteins (HSPs) which are non-covalently bound to peptides as HSP-peptide complexes have been shown to be capable of inducing T-cell mediated responses to tumor antigens, see for example Udono et al. “Heat shock protein 70-associated peptides elicit specific cancer immunity” in
Journal of Experimental Medicine
(1993) 178: 1391-1396; and Tamura et al. “Immunotherapy of tumors with autologous tumor-derived heat shock protein preparations” in
Science
(1997), 278:117-120. HSP-peptide complexes have also been shown to be capable of inducing T-cell mediated responses to viral antigens as described in Roman et al., “Synthetic peptides non-covalently bound to bacterial HSP 70 elicit peptide specific T-cell responses in vivo in
Immunology
(1996), 88:487-492. HSPs covalently bound to antigens as fusion proteins have also be shown to elicit a T-cell specific response, see for example, Suzue, “Heat shock proteins as vehicles for antigen delivery into the major histocompatibility complex I presentation pathway” in
Proceedings of the National Academy of Sciences
(1997), 94:13146-13151. HSPs have also been shown to be important in the recognition structure for NK cells, see for example Multhoff et al., “Heat shock protein 72 on tumor cells: a recognition structure for NK cells” in
The Journal of Immunology
(1997), 158:4341-4350 and gamma delta T-cells, see for example Wei et al., “Induction of autologous tumor killing by heat treatment of fresh human tumor cells: involvement of &ggr;&dgr; T cells and heat shock protein 70, in Cancer Research (1996), 56:1104-1110.
Toxins linked to antibodies have been used to specifically target cancer cells as described by Siegall et al., “Immunotoxins as cancer chemotherapeutic-agents” in
Drug Development Research
, v. 34(#2), (Feb. 1995), pp. 210-219. Toxins have also been linked as a fusion protein to human granulocyte-macrophage colony-stimulating factor by Burbage et al., “Ricin fusion toxin targeted to human granulocyte-macrophage colony-stimulating factor-receptor is selectively toxi to acute myeloid-leukemia cells” in
Leukemia Research
, v. 21 (#7), (Jul. 1997). pp. 681-690; and Frankel et al. “112 fused to lectin-deficient ricin is toxic to human leukemia -cells expressing the 112 receptor” in
Leukemia
, v. 11(#1), (Jan. 1997), pp. 22-30.
However, no one has investigated the possibility of using heat shock proteins as cell-specific carriers of toxins and agents capable of inhibiting the cellular function of immune cells. Since HSPs appear to be recognized by a variety of immune cells, toxin or cellular pathyway inhibitors linked to heat shock proteins may be a very useful tool.
The present invention relies on the fact that heat shock proteins are recognized by numerous cells in the immune system. The cells that are known to respond in the presence of heat shock proteins include T-cells, macrophages, dendritic cells, and B-cells. The toxin linked heat shock proteins of the present invention may provide a means to deplete these cells in circumstances where it is desirable to do so. Although it is not clearly understood at the present time which cells react to specific heat shock proteins, it is conceivable th
Moseley Pope L.
Wallen Erik
Delacroix-Muirhei C.
Jagtiani + Guttag
Jones Dwayne C.
University of New Mexico
LandOfFree
Methods for using heat shock proteins does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Methods for using heat shock proteins, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods for using heat shock proteins will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2869169