Armed dual CAR-T compositions and methods for cancer immunotherapy
The disclosure provides, in various embodiments, polynucleotides and vectors comprising sequences encoding a mono-specific or a bi-specific CAR that is capable of binding to a first TAA, or a T-cell engager that is capable of binding to CD3 and a second TAA, or a combination thereof. The disclosure also provides, in various embodiments, T lymphocytes comprising one or more of the polynucleotides or vectors; compositions (e.g., pharmaceutical compositions) and kits comprising one or more of the T lymphocytes; methods of treating a cancer in mammalian subject (e.g., a human), and methods of inducing T cell-mediated cytolysis of cancer cells (e.g., solid tumor cells).
1. A polynucleotide comprising a sequence encoding a polypeptide comprising the amino acid sequence set forth in any one of SEQ ID NOs: 35-38.
2. A vector comprising the polynucleotide of claim 1 .
3. A fusion protein encoded by the polynucleotide of claim 1 .
4. A host cell comprising the polynucleotide of claim 1 .
5. The polynucleotide of claim 1 , wherein the polynucleotide encodes a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 35.
6. The polynucleotide of claim 1 , wherein the polynucleotide encodes a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 36.
7. The polynucleotide of claim 1 , wherein the polynucleotide encodes a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 37.
8. The polynucleotide of claim 1 , wherein the polynucleotide encodes a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 38.
9. A T lymphocyte comprising the polynucleotide of claim 1 .
10. A composition comprising the T lymphocyte of claim 9 .
11. A pharmaceutical composition comprising the composition of claim 10 and a pharmaceutically acceptable carrier.