IL2 and cancer: In cancer therapy, prioritizing the second form and avoiding the first form is crucial, to decouple pleiotropic effects, thereby enhancing efficacy and reducing toxicity.25,245,251 Native IL-2 consists of four helices connected by loops, forming a N-terminal helix (H1), long loop, helix (H2), short loop, helix 3 (H3), long loop, and C-terminal helix (H4) architecture.