Compositions and methods for treatment of liquid cancers

A method for producing a CD7 CAR-expressing immune cell or population of CAR-expressing immune cells having reduced immunogenicity, the method comprising

• a) contacting a target polynucleotide in an immune cell or population of immune cells with a guide polynucleotide and a base editor comprising a fusion protein comprising a nucleic acid programmable DNA binding protein (napDNAbp) and a deaminase domain or a base editor system comprising a guide polynucleotide and a nucleic acid programmable DNA binding protein (napDNAbp) and a deaminase domain;
• b) introducing by nucleobase modification a mutation that reduces or eliminates the expression of a CD7 antigen into the immune cell or the population of immune cells;
• c) introducing by nucleobase modification a mutation that reduces or eliminates the expression of at least one polypeptide selected from the group consisting of CD3e, TRAC, LAG-3, FAS, CIITA, TRBC1, TRBC2, CD52, B2M, and PDC1/PD-1 into the immune cells or the population of immune cells;
• and
• d) expressing in the immune cell or population of immune cells a chimeric antigen receptor that targets the CD7 antigen thereby producing a CAR-expressing immune cell or population of CAR-expressing immune cells having reduced immunogenicity, wherein the chimeric antigen receptor that targets the CD7 antigen comprises or consists of SEQ ID NO:
• 113.