Gene-regulating compositions and methods for improved immunotherapy

A method of treating cancer in a subject in need thereof, the method comprising:

• administering to the subject a composition comprising a therapeutically effective amount of modified human tumor infiltrating lymphocytes (TILs) that comprise an insertion, deletion, or mutation in an endogenous SOCS1 gene, wherein endogenous SOCS1 gene expression is reduced in the modified human TILs, relative to unmodified human TILs obtained from the subject.

A method of treating a solid tumor in a subject in need thereof, the method comprising:

• selecting a subject who has a solid tumor that is insensitive to, or resistant to, is resistant to treatment with an immune checkpoint inhibitor;
• and
• administering to the subject a composition comprising about 1×107 and about 1×1012 modified human tumor infiltrating lymphocytes (TILs) that comprise an insertion, deletion, or mutation in an endogenous SOCS1 gene, wherein endogenous SOCS1 gene expression is reduced in the modified human TILs, relative to unmodified human TTLs obtained from the subject.