Despite the aforementioned efforts and significant antitumor effects reported in preclinical studies, intermediate-affinity IL-2R-targeting engineered IL-2 has achieved disappointing results in the treatment of cancer patients in clinical trials (reviewed in86), with the example of negative data from the PIVOT IO-001 phase 3 trial of NKTR-214 by Nektar and Bristol Myers Squibb87. This evidence concerns the gene IL2RA and cancer.