Patent · US6319494B1 · B1 · US
Chimeric chains for receptor-associated signal transduction pathways
- (11) Publication number
- US6319494B1
- (21) Application number
- 08/479,737
- (22) Filing date
- 1995-06-07
- (30) Priority date
- 1990-12-14
- (43) Publication date
- 2001-11-20
- (45) Date of grant
- 2001-11-20
- (51) IPC
- C07K 14/725; C07K 14/73; C07K 14/735
- (52) CPC
- C07K Peptides: 14/70514, 14/7051, 14/70535, 2319/00
- (73) Assignee
- Cell Genesys Inc
- (72) Inventors
- Daniel J. Capon; Arthur Weiss; Brian A. Irving; Margo R. Roberts; Krisztina Zsebo
- (54) Title
- Chimeric chains for receptor-associated signal transduction pathways
- (57) Abstract
Chimeric proteins and DNA encoding chimeric proteins are provided, where the chimeric proteins are characterized by an extracellular domain capable of binding to a ligand in a non-MHC restricted manner, a transmembrane domain and a cytoplasmic domain capable of activating a signaling pathway. The extracellular domain and cytoplasmic domain are not naturally found together. Binding of ligand to the extracellular domain results in transduction of a signal and activation of a signaling pathway in the cell, whereby the cell may be induced to carry out various functions relating to the signalling pathway. A wide variety of extracellular domains may be employed as receptors, where such domains may be naturally occurring or synthetic. The chimeric DNA may be used to modify lymphocytes as well as hematopoietic stem cells as precursors to a number of important cell types.
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Claims (2)
- A method for treating a viral disease or a malignancy in a mammal, wherein cells of said mammal express viral or tumor antigens, comprising introducing modified T cells into said mammal wherein said modified T cells comprise a chimeric DNA encoding a membrane bound protein comprising in the N-terminal to C-terminal direction: a single chain antibody domain that binds specifically to said viral or tumor antigen; a transmembrane domain; and a cytoplasmic signal-transducing domain obtained from ζ wherein when said single chain antibody domain binds to said viral or tumor antigen on said cell, said modified T cells kill the cells expressing said viral or tumor antigen.
- The method of claim 1 wherein said single-chain antibody is reactive with HIV.
Description
1. Technical Field
The field of this invention is the use of chimeric surface membrane proteins for signal transduction.
2. Background
Regulation of cell activities is frequently achieved by the binding of the ligand to a surface membrane receptor. The formation of the complex with the extracellular portion of the receptor results in a change in conformation with the cytoplasmic portion of the receptor undergoing a change which results in a signal being transduced in the cell. In some instances, the change in the cytoplasmic portion results in binding to other proteins, where the other proteins are activated and may carry out various functions. In some situations, the cytoplasmic portion is autophosphorylated or phosphorylated, resulting in a change in its activity. These events are frequently coupled with secondary messengers, such as calcium, cyclic adenosine monophosphate, inositol phosphate, diacylglycerol, and the like. The binding of the ligand results in a particular signal being induced.
There are a number of instances, where one might wish to have a signal induced by virtue of employing a different ligand. For example, one might wish to activate particular T-cells, where the T-cells will then be effective as cytotoxic agents, or activating agents by secretion of interleukins, colony stimulating factors or other cytokines, which results in the stimulation of another cell. The ability of the T-cell receptor to recognize antigen is restricted by the nature of Major Histocompatibility Complex (MHC) antigens on the surface of the host cell.
Citations (5)
- WO1992015322A1
- WO1993019163A1
- WO1995002686A1
- WO1995006409A1
- WO1995021528A1
Record as JSON
{
"publication_number": "US6319494B1",
"country": "US",
"kind": "B1",
"title": "Chimeric chains for receptor-associated signal transduction pathways",
"abstract": "Chimeric proteins and DNA encoding chimeric proteins are provided, where the chimeric proteins are characterized by an extracellular domain capable of binding to a ligand in a non-MHC restricted manner, a transmembrane domain and a cytoplasmic domain capable of activating a signaling pathway. The extracellular domain and cytoplasmic domain are not naturally found together. Binding of ligand to the extracellular domain results in transduction of a signal and activation of a signaling pathway in the cell, whereby the cell may be induced to carry out various functions relating to the signalling pathway. A wide variety of extracellular domains may be employed as receptors, where such domains may be naturally occurring or synthetic. The chimeric DNA may be used to modify lymphocytes as well as hematopoietic stem cells as precursors to a number of important cell types.",
"claims": [
"1. A method for treating a viral disease or a malignancy in a mammal, wherein cells of said mammal express viral or tumor antigens, comprising introducing modified T cells into said mammal wherein said modified T cells comprise a chimeric DNA encoding a membrane bound protein comprising in the N-terminal to C-terminal direction: a single chain antibody domain that binds specifically to said viral or tumor antigen; a transmembrane domain; and a cytoplasmic signal-transducing domain obtained from ζ wherein when said single chain antibody domain binds to said viral or tumor antigen on said cell, said modified T cells kill the cells expressing said viral or tumor antigen.",
"2. The method of claim 1 wherein said single-chain antibody is reactive with HIV."
],
"description_excerpt": "1. Technical Field\n\nThe field of this invention is the use of chimeric surface membrane proteins for signal transduction.\n\n2. Background\n\nRegulation of cell activities is frequently achieved by the binding of the ligand to a surface membrane receptor. The formation of the complex with the extracellular portion of the receptor results in a change in conformation with the cytoplasmic portion of the receptor undergoing a change which results in a signal being transduced in the cell. In some instances, the change in the cytoplasmic portion results in binding to other proteins, where the other proteins are activated and may carry out various functions. In some situations, the cytoplasmic portion is autophosphorylated or phosphorylated, resulting in a change in its activity. These events are frequently coupled with secondary messengers, such as calcium, cyclic adenosine monophosphate, inositol phosphate, diacylglycerol, and the like. The binding of the ligand results in a particular signal being induced.\n\nThere are a number of instances, where one might wish to have a signal induced by virtue of employing a different ligand. For example, one might wish to activate particular T-cells, where the T-cells will then be effective as cytotoxic agents, or activating agents by secretion of interleukins, colony stimulating factors or other cytokines, which results in the stimulation of another cell. The ability of the T-cell receptor to recognize antigen is restricted by the nature of Major Histocompatibility Complex (MHC) antigens on the surface of the host cell.",
"cpc": [
"C07K 14/70514",
"C07K 14/7051",
"C07K 14/70535",
"C07K 2319/00"
],
"ipc": [
"C07K 14/725",
"C07K 14/73",
"C07K 14/735"
],
"assignees": [
"Cell Genesys Inc"
],
"inventors": [
"Daniel J. Capon",
"Arthur Weiss",
"Brian A. Irving",
"Margo R. Roberts",
"Krisztina Zsebo"
],
"filing_date": "1995-06-07",
"publication_date": "2001-11-20",
"grant_date": "2001-11-20",
"priority_date": "1990-12-14",
"application_number": "US-47973795-A",
"family_id": "27399092",
"cited_by_count": 354,
"citations": [
"WO1992015322A1",
"WO1993019163A1",
"WO1995002686A1",
"WO1995006409A1",
"WO1995021528A1"
]
}
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