Chimeric receptor molecules for delivery of co-stimulatory signals
First Claim
1. A DNA encoding a chimeric membrane-bound protein, said protein comprising in the N-terminal to C-terminal direction:
- a signal sequence;
an extracellular binding domain of a surface membrane or secreted protein that binds specifically to at least one ligand;
a transmembrane domain; and
a cytoplasmic domain of CD2 or CD28;
wherein said extracellular domain is not obtained from CD2 or CD28, and when said DNA is placed in a selected host cell under conditions suitable for expression, said chimeric membrane-bound protein is expressed and co-stimulates effector function signaling in said host cell upon binding of a ligand to the extracellular domain.
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Abstract
The present invention is directed to novel chimeric co-stimulatory receptor proteins and DNA sequences encoding these proteins. The chimeric receptors comprise at least three domains in a single chain molecule: an extracellular ligand binding domain, a transmembrane domain and a cytoplasmic co-stimulatory effector function signaling domain that acts synergistically with an effector function signal in the host cell. Novel hybrid co-stimulatory receptor proteins include a second cytoplasmic effector function signaling domain. The invention further relates to expression cassettes containing the nucleic acids encoding the novel chimeric receptors, to host cells expressing the novel chimeric receptors and to methods of using the receptors to co-stimulate effector functions in the cells and for using cells expressing the receptors for treatment of cancer, disease and viral infections.
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Citations
25 Claims
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1. A DNA encoding a chimeric membrane-bound protein, said protein comprising in the N-terminal to C-terminal direction:
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a signal sequence; an extracellular binding domain of a surface membrane or secreted protein that binds specifically to at least one ligand; a transmembrane domain; and a cytoplasmic domain of CD2 or CD28; wherein said extracellular domain is not obtained from CD2 or CD28, and when said DNA is placed in a selected host cell under conditions suitable for expression, said chimeric membrane-bound protein is expressed and co-stimulates effector function signaling in said host cell upon binding of a ligand to the extracellular domain. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 21, 22)
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11. A DNA encoding a hybrid chimeric membrane-bound protein, said protein comprising in the N-terminal to C-terminal direction;
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a signal sequence; an extracellular binding domain of a surface membrane or secreted protein that binds specifically to at least one ligand; a transmembrane domain; a cytoplasmic domain of CD2 or CD28; and a cytoplasmic effector function signaling domain; wherein said extracellular domain is not obtained from CD2 or CD28, and when said DNA is placed in a selected host cell under conditions suitable for expression, said hybrid chimeric membrane-bound protein is expressed and initiates an effector function signal and a co-stimulatory effector function signal upon binding of a ligand to said extracellular domain. - View Dependent Claims (12, 13, 14, 15)
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16. A DNA encoding a hybrid chimeric membrane-bound protein, said protein comprising in the N-terminal to C-terminal direction;
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a signal sequence; an extracellular binding domain of a surface membrane or secreted protein that binds specifically to at least one ligand; a transmembrane domain; a cytoplasmic effector function signaling domain; and a cytoplasmic domain of CD2 or CD28; wherein said extracellular domain is not obtained from CD2 or CD28, and when said DNA is placed in a selected host cell under conditions suitable for expression, said hybrid chimeric membrane-bound protein initiates an effector function signal and a co-stimulatory effector function signal upon binding of a ligand to said extracellular domain. - View Dependent Claims (17, 18, 19, 20)
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23. A chimeric co-stimulatory receptor protein comprising in the N-terminal to C-terminal direction;
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an extracellular ligand binding domain that binds specifically to at least one ligand; a transmembrane domain; and a cytoplasmic co-stimulatory signaling domain of CD2 or CD28; wherein said extracellular domain is not obtained from CD2 or CD28, and when said chimeric co-stimulatory protein is expressed as a membrane-bound receptor in a host cell under conditions suitable for expression said membrane-bound receptor initiates a co-stimulatory effector function signal in said host cell upon binding of a ligand to the extracellular domain.
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24. A hybrid chimeric co-stimulatory receptor protein comprising in the N-terminal to C-terminal direction;
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an extracellular ligand binding domain that binds specifically to at least one ligand; a transmembrane domain; a cytoplasmic co-stimulatory signaling domain of CD2 or CD28; and a cytoplasmic effector function signaling domain, wherein said extracellular domain is not obtained from CD2 or CD28, and when said hybrid chimeric co-stimulatory protein is expressed as a membrane-bound receptor in a host cell under conditions suitable for expression, said membrane-bound receptor initiates an effector function signal and a co-stimulatory effector function signal in said host cell upon binding of a ligand to the extracellular domain.
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25. A hybrid chimeric co-stimulatory receptor protein comprising in the N-terminal to C-terminal direction;
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an extracellular ligand binding domain that binds specifically to at least one ligand; a transmembrane domain; a cytoplasmic effector function signaling domain; and a cytoplasmic co-stimulatory signaling domain of CD2 or CD28; wherein said extracellular domain is not obtained from CD2 or CD28, and when said hybrid chimeric co-stimulatory protein is expressed as a membrane-bound receptor in a host cell under conditions suitable for expression said membrane-bound receptor initiates an effector function signal and a co-stimulatory effector function signal in said host cell upon binding of a ligand to the extracellular domain.
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Specification