Chimeric receptors with 4-1BB stimulatory signaling domain
First Claim
1. A chimeric receptor comprising an extracellular ligand binding domain, a transmembrane domain, and a cytoplasmic domain, wherein said cytoplasmic domain comprises the signaling domain of 4-1BB.
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Abstract
The present invention relates to a chimeric receptor capable of signaling both a primary and a co-stimulatory pathway, thus allowing activation of the co-stimulatory pathway without binding to the natural ligand. The cytoplasmic domain of the receptor contains a portion of the 4-1BB signaling domain. Embodiments of the invention relate to polynucleotides that encode the receptor, vectors and host cells encoding a chimeric receptor, particularly including T cells and natural killer (NK) cells and methods of use. Also included is a method for obtaining an enriched population of NK cells from a mixed population of NK cells and T cells.
152 Citations
26 Claims
- 1. A chimeric receptor comprising an extracellular ligand binding domain, a transmembrane domain, and a cytoplasmic domain, wherein said cytoplasmic domain comprises the signaling domain of 4-1BB.
- 12. A chimeric receptor having a cytoplasmic domain comprising the signaling domain of 4-1BB.
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16. A method of enhancing T lymphocyte or natural killer cell activity of an individual by introducing into said individual a T lymphocyte or natural killer cell comprising a chimeric receptor having a cytoplasmic domain comprising the signaling domain of 4-1BB.
- 17. A method for treating an individual suffering from cancer by introducing into said individual a T lymphocyte or natural killer cell comprising a chimeric receptor wherein said chimeric receptor comprises an extracellular ligand binding domain, a transmembrane domain, and a cytoplasmic domain, wherein said cytoplasmic domain comprises the signaling domain of 4-1BB.
- 22. A cell line comprising cells that activate natural killer (NK) cells, lack or poorly express major histocompatibility complex I molecules and do not activate T lymphocytes wherein such NK activating cells express membrane bound interleukin-15 and a co-stimulatory factor ligand.
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26. A method of expanding natural killer (NK) cells which comprises culturing a population of cells comprising NK cells with a cell line that activates NK cells, wherein the cell line that activates NK cells expresses membrane bound interleukin-15 and a co-stimulatory factor ligand.
Specification