Chimeric antigen receptors with enhanced tumor infiltration
OwnerAlan F. List, Sheng Weiinventors
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Abstract
Disclosed herein are CAR-T cells with enhanced tumor infiltration. As disclosed herein, infiltrating lymphocytes (T and NK) within tumor tissue are absent of CX3CR1, a key chemokine receptor specific for lymphocytes. Therefore, disclosed herein are CAR-T cells that co-express CX3CR1 to enhance the infiltration of CAR-T cells into the tumor tissue. Also disclosed herein are CAR-T cells that co-express IL-15 in order to activate infiltration of NK cell. In some embodiments, the disclosed CAR-T cells express both CX3CR1 and IL-15 in combination with the CAR polypeptide. In some embodiments, the disclosed CAR-T cells further express EGFR in combination with the CAR polypeptide.
Claims20
An polynucleotide comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR) polypeptide, wherein the polynucleotide further comprises:
- a nucleic acid sequence encoding a CX3CR1 protein;
- a nucleic acid sequence encoding an IL-15 protein;
- a nucleic acid sequence encoding an EGFR protein;
- or any combination thereof.
A cell comprising a chimeric antigen receptor (CAR) polypeptide, wherein the cell further comprises:
- a recombinant a CX3CR1 protein;
- a recombinant IL-15 protein;
- a recombinant EGFR protein;
- or any combination thereof.
The method of acclaim 18, further comprising administering to the subject a checkpoint inhibitor.
Dependencies are inferred from the claim text.