Antitumor immunity induced by antibody-based natural killer cell engager therapeutics armed with not-alpha IL-2 variant

We report here the design of new antibody-based natural killer cell engager therapeutics (ANKET), single tetraspecific molecules engaging the NK cell activating receptors NKp46 and CD16, the ß chain of the interleukin-2 receptor (IL-2R) and a tumor-associated antigen (TAA). Overall design: We performed transcriptome analysis on NK cells purified from blood and activated with tetraspecific ANKET, trispecific aNKp46/Fc/aCD20, the Fc-enhanced anti-CD20 mAb obinutuzumab or an IL-2v polypeptide (IL2v/IC/Fc null/IC) in the presence of CD20+ tumor target cells