MUC16 specific chimeric antigen receptors and uses thereof
Provided herein are chimeric antigen receptors (CARs) for cancer therapy, and more particularly, CARs containing a scFv from an anti-MUC16 monoclonal antibody. Provided are immune effector cells containing such CARs, and methods of treating proliferative disorders.
1. An isolated nucleic acid encoding a chimeric antigen receptor (CAR), wherein the CAR comprises a polypeptide having the amino acid sequence of SEQ ID NO: 31.
2. The isolated nucleic acid of claim 1 , further encoding a truncated epidermal growth factor receptor.
3. The isolated nucleic acid of claim 2 , wherein the truncated epidermal growth factor receptor is HER1t and comprises a polypeptide having the amino acid sequence of SEQ ID NO: 65 or SEQ ID NO: 66.
4. A vector comprising a backbone and a nucleic acid encoding: (1) a truncated epidermal growth factor receptor comprising at least one of HER1t, HER1t−1, or a functional variant thereof: (2) a cytokine; and (3) a chimeric antigen receptor (CAR) comprising a polypeptide having the amino acid sequence of SEQ ID NO: 31.
5. The vector of claim 4 , wherein the cytokine is IL-15 or IL-12.
6. The vector of claim 4 , wherein the vector is a lentivirus vector, a retroviral vector, or a non-viral vector.
7. The vector of claim 5 , wherein the IL-15 is membrane bound IL-15.
8. The vector of claim 7 , wherein the membrane bound IL-15 comprises a nucleotide sequence that encodes a polypeptide having the amino acid sequence of SEQ ID NO: 69.
9. The vector of claim 4 , further comprising a nucleotide sequence encoding a self-cleaving Thosea asigna virus (T2A) peptide.
10. An immune effector cell comprising the vector of claim 4 .
11. The immune effector cell of claim 10 , wherein the cell is a T cell, a Natural Killer (NK) cell, a cytotoxic T lymphocyte (CTL), or a regulatory T cell.