IL2 and cancer: In a recent exploration of IL-2 engineering for cancer therapy, Christopher Garcia’s group developed an innovative orthogonal mouse IL-2 cytokine-receptor pair system, by using yeast display to introduce mutations in both the cytokine and the receptor.341 These specialized pairs are designed around the principle of receptor-ligand orthogonalization, allowing the receptor to respond to mouse orthogonal IL-2 (ortho-mIL-2), while remaining unresponsive to the wild-type mouse IL-2 (Fig. 10f).