Modification of IL-2 for anticancer therapy. (A) Mutations in CD122 (IL-2Rβ)-binding regions of IL-2 superkines (Super-IL-2) increase binding affinity of IL-2 for IL-2Rβ than CD25 (IL-2Rα). (B) The conjugation with antibody to tumor-associated antigens (TAAs) or collagen-binding domain delivers IL-2 to tumor sites. (C) The IL-2 complex with a neutralizing antibody clone S4B6 predominantly targets cells expressing dimeric IL-2Rβγ. (D) Fc-fused IL-2 has a prolonged serum half-life. (E) Fc-fused mutant IL-2 shows an increased half-life with enhanced binding affinity for IL-2Rβ. (F) The conjugation of polyethylene glycol (PEG) shows increased IL-2 persistence with an inhibited IL-2Rα binding. Figure created with BioRender.com.