Immune cells with chimeric antigen receptors or chimeric autoantibody receptors

A method of making a chimeric antigen receptor (CAR)-immune cell, the method comprising administering to a subject:

• a first nucleic acid encoding an enzyme capable of performing targeted genomic integration, wherein the first nucleic acid is RNA, and
• a second, non-viral nucleic acid encoding a donor DNA comprising a chimeric CAR and flanked by ends recognized by the enzyme capable of performing targeted genomic integration,
• wherein the administration uses lipid nanoparticles (LNPs) capable of directing the first and second nucleic acids to an immune cell, to thereby create a CAR-immune cell,
• wherein the immune cell is selected from a T cell, a macrophage, and a natural killer (NK) cell.

A method of making a chimeric autoantibody receptor (CAAR)-immune cell, the method comprising:

• obtaining a cell from a sample obtained from a subject, the sample comprising T cells or T cell progenitors;
• and
• transfecting the cell with
• a first nucleic acid encoding an enzyme capable of performing targeted genomic integration, wherein the first nucleic acid is RNA, and
• a second, non-viral nucleic acid encoding a donor DNA comprising a chimeric CAAR comprising an autoantigen or a fragment thereof, and flanked by ends recognized by the enzyme capable of performing targeted genomic integration, to thereby create a transfected CAAR-immune cell,
• wherein the immune cell is selected from a T cell, a macrophage, and a natural killer (NK) cell.

A method of making a chimeric autoantibody receptor (CAAR)-immune cell, the method comprising administering to a skin cell in a subject:

• a first nucleic acid encoding an enzyme capable of performing targeted genomic integration, wherein the first nucleic acid is RNA, and
• a second, non-viral nucleic acid encoding a donor DNA comprising a chimeric CAAR comprising an autoantigen or a fragment thereof, and flanked by ends recognized by the enzyme capable of performing targeted genomic integration,
• wherein the administration is performed via intradermal or subcutaneous delivery and using lipid nanoparticles (LNPs) capable of directing the first and second nucleic acids to an immune cell, to thereby create a CAR-immune cell,
• wherein the immune cell is selected from a T cell, a macrophage, and a natural killer (NK) cell.

The method of claim 94, wherein the end sequences are selected from nucleotide sequences having at least about 90% identity to SEQ ID NO:

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