IL2 and colonic neoplasm: Using orthogonal gene engineering, allowing T cells to express ortho IL-2Rβ, so that they can be selectively targeted by ortho IL-2 [249], or allowing T cells to secrete an IL-2 variant that can bind to IL-2Rβγ and the alarmin IL-33, can make adoptively transferred engineered T cells far from exhaustion and maintain superior effector function, ultimately improving the survival rate in mouses bearing advanced colon tumor [250].