Back to results
US 2026/0216246 A1Published application
Chimeric antigen receptor constructs with optimized intracellular domains for natural killer cells
OwnerReshmi Parameswaran, Derek Wonginventors
Life of this patent
Estimating the term…
Abstract
A chimeric antigen receptor (CAR) for NK cells includes an extracellular antigen binding domain, a transmembrane domain, and at least one an intracellular signaling domain.
Claims26
1:
- A chimeric antigen receptor (CAR) comprising:
- an extracellular antigen binding domain, a transmembrane domain, and at least one an intracellular signaling domain, wherein the intracellular signaling domain includes a CD16A intracellular signaling domain, γc intracellular signaling domain, 2B4 intracellular signaling domain, CD28 intracellular signaling domain, 41 BB intracellular signaling domain, DAP10 intracellular signaling domain, DAP12 intracellular signaling domain, and/or combinations thereof.
2:
- The CAR of claim 1, wherein the transmembrane is selected from a CD28 transmembrane domain, a CD16a transmembrane domain, a 2B4 transmembrane domain, or a NKG2D transmembrane domain.
3:
- The CAR of claim 2, wherein the CD28 transmembrane comprises an amino acid sequence at least about 90% identical to SEQ ID NO:
- 10;
- the CD16a transmembrane comprises an amino acid sequence at least about 90% identical to SEQ ID NO:
- 22;
- the 2B4 transmembrane comprises an amino acid sequence at least about 90%, identical to SEQ ID NO:
- 24;
- or
- the NKG2D transmembrane comprises an amino acid sequence at least about 90% identical to SEQ ID NO:
- 26.
6 more elements
4-6. (canceled)
7:
- The CAR of claim 1, wherein the CD16a intracellular signaling domain comprises an amino acid sequence at least about 90% identical to SEQ ID NO:
- 12;
- or
- the γc intracellular signaling domain comprises an amino acid sequence at least about 90% identical to SEQ ID NO:
- 20.
2 more elements
(canceled)
9:
- The CAR of claim 1, further comprising the 2B4 intracellular signaling domain and a CD3ζ intracellular domain.
10:
- The CAR of claim 9, wherein the 2B4 intracellular signaling domain comprises an amino acid sequence at least about 90% identical to SEQ ID NO:
- 14;
- and the CD3ζ intracellular domain includes an amino acid sequence at least about 90% identical to SEQ ID NO:
- 16.
1 more element
(canceled)
12:
- The CAR of claim 1, further comprising at least one of an extracellular spacer or hinge domain.
13:
- The CAR of claim 12, wherein the hinge domain is an IgG1 hinge domain.
14:
- The CAR of claim 12, wherein the spacer comprises an amino acid sequence at least about 90% identical to SEQ ID NO:
- 6;
- or
- the hinge domain comprises an amino acid sequence at least about 90% identical to SEQ ID NO:
- 8.
2 more elements
(canceled)
16:
- The CAR of claim 1, further comprising a signal peptide.
17:
- The CAR of claim 9, comprising the extracellular antigen binding domain, a spacer, an IgG1 hinge domain, the transmembrane domain, the CD16a intracellular signaling domain, the 2B4 intracellular signaling domain, and the CD3ζ intracellular domain.
18:
- The CAR of claim 9, comprising the extracellular antigen binding domain, a spacer, an IgG1 hinge domain, the transmembrane domain, γc intracellular signaling domain, the 2B4 intracellular signaling domain, and the CD3ζ intracellular domain.
19:
- The CAR of claim 9, comprising the extracellular antigen binding domain, a spacer, an IgG1 hinge domain, the transmembrane domain, the CD28 intracellular signaling domain, the 2B4 intracellular signaling domain, and the CD3ζ intracellular domain.
20:
- The CAR of claim 1, comprising the extracellular antigen binding domain, a spacer, an IgG1 hinge domain, the transmembrane domain, the 2B4 intracellular signaling domain, the 41 BB intracellular signaling domain, and a CD3ζ intracellular domain.
21:
- The CAR of claim 1, comprising the extracellular antigen binding domain, a spacer, an IgG1 hinge domain, the transmembrane domain, the 2B4 intracellular signaling domain, the DAP10 intracellular signaling domain, the DAP12 intracellular signaling domain, and a CD3ζ intracellular signaling domain.
22:
- The CAR of claim 1, wherein the extracellular antigen binding domain comprises a polypeptide that binds to a receptor of BAFF.
23:
- The CAR of claim 22, wherein the receptor of BAFF is selected from the group consisting of B-cell maturation antigen, transmembrane activator and CAML interactor, and BAFF receptor.
24:
- The CAR of claim 1, wherein the extracellular antigen binding domain comprises a BAFF ligand.
25:
- The CAR of claim 24, wherein the BAFF ligand comprises an amino acid sequence at least about 90% identical to SEQ ID NO:
- 4.
26-45. (canceled)
46:
- A natural killer cell comprising the CAR of claim 1.
47-61. (canceled)
Dependencies are inferred from the claim text.