| 摘要 |
Provided are compositions and methods relating to regulatable chimeric antigen receptors (RCARs), natural killer cell receptor CARs (NKR-CARs), and regulatable NKR-CARs (RNKR-CARs), where the intracellular signaling or proliferation of the RCAR or RNKR-CAR can be controlled to optimize the use of an RCAR/NKR-CAR- or RNKR-CAR-expressing cell to provide an immune response. Cells can be engineered to express a RNKR-CAR or to express a RCAR and a NKR-CAR (e.g., inhibitory NKR-CAR). For example, a RCAR or RNKR-CAR can comprise a dimerization switch that, upon the presence of a dimerization molecule, can couple an intracellular signaling domain to an extracellular recognition element, e.g., an antigen binding domain, an inhibitory counter ligand binding domain, or costimulatory ECD domain. An RCAR or RNKR-CAR can be engineered to include an appropriate antigen binding domain that is specific to a desired antigen target and used in the treatment of a disease. |
| 主权项 |
1. A regulatable natural killer receptor CAR (RNKR-CAR), e.g., an isolated NKR-CAR, wherein the RNKR-CAR comprises:
c) an antigen binding member, comprising
a binding domain element,a transmembrane domain,a first switch domain, andoptionally, a NKR cytoplasmic domain, e.g., selected from Table 24,
wherein the binding domain element comprises an antigen binding domain, an inhibitory extracellular domain, e.g., selected from Table 4, or a costimulatory extracellular domain, e.g., selected from Table 5; and d) an intracellular signaling member comprising
a second switch domain,a NKR cytoplasmic domain e.g., selected from Table 24, or an intracellular signaling domain, e.g., a primary signaling domain, e.g., selected from Table 1, e.g., a DAP12 signaling domain, or a CD3zeta signaling domain, andoptionally, a transmembrane domain or a membrane tether. |
