Cells expressing an anti-mesothelin car

A polynucleotide comprising

• (i) a nucleotide sequence encoding a chimeric antigen receptor (CAR), wherein the CAR comprises an antigen-binding domain that specifically binds human mesothelin, wherein the antigen-binding domain comprises a variable heavy (VH) domain and a variable light (VL) domain, wherein the VH comprises a VH-complementarity determining region 1 (VH-CDR1) comprising the amino acid sequence set forth in SEQ ID NO:
• 1, a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
• 2, a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
• 3;
• and wherein the VL comprises a VL-CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
• 4, a VL-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
• 5, and a VL-CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
• 6;
• and 3
• (ii) a second nucleotide sequence encoding an armor protein, wherein the armor protein comprises:
• (a) an IL-15Rβ polypeptide,
• (b) an IL-15Rα polypeptide,
• (c) an IL-15Rα polypeptide tethered to an IL-15 polypeptide,
• (d) an IL-15 polypeptide, or
• (e) any combination thereof.

A chimeric antigen receptor comprising an antigen-binding domain that specifically binds human mesothelin, wherein the antigen-binding domain comprises a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID NO:

• 1, a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
• 2, a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
• 3, a VL-CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
• 4, a VL-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
• 5, and a VL-CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
• 6;
• and
• (i) a hinge region comprising an amino acid sequence having at least about 90% sequence identity to the sequence set forth in SEQ ID NO:
• 9,
• (ii) a transmembrane domain comprising an amino acid sequence having at least about 90% sequence identity to the sequence set forth in SEQ ID NO:
• 10.
• (iii) a costimulatory domain comprising an amino acid sequence having at least about 90% sequence identity to the sequence set forth in SEQ ID NO:
• 11,
• (iv) an intracellular signalling domain comprising an amino acid sequence having at least about 90% sequence identity to the sequence set forth in SEQ ID NO:
• 12, or
• (v) any combination of (i) to (iv).

An engineered innate lymphoid cell comprising:

• (a) a chimeric antigen receptor (CAR), wherein the CAR comprises
• (i) an antigen-binding domain that specifically binds human mesothelin, wherein the antigen-binding domain comprises a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
• 1, a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
• 2, a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
• 3, a VL-CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
• 4, a VL-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
• 5, and a VL-CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
• 6;
• (ii) a hinge region comprising the amino acid sequence set forth in SEQ ID NO:
• 9;
• (iii) a transmembrane domain comprising the amino acid sequence set forth in SEQ ID NO:
• 10;
• (iv) a costimulatory domain comprising the amino acid sequence set forth in SEQ ID NO:
• 11;
• and
• (v) an intracellular signaling domain comprising the amino acid sequence set forth in SEQ ID NO:
• 12;
• and
• (b) an armor protein, wherein the armor protein comprises:
• (i) an IL-2Rβ polypeptide comprising the amino acid sequence set forth in SEQ ID NO:
• 15;
• (ii) a linker comprising the amino acid sequence set forth in SEQ ID NO:
• 18;
• and
• (iii) an IL-15Rα polypeptide tethered to an IL-15 polypeptide, wherein the IL-15Rα polypeptide comprises the amino acid sequence set forth in SEQ ID NO:
• 17, and wherein the IL-15 polypeptide comprises the amino acid sequence set forth in SEQ ID NO:
• 16.