Anti-CD20-IL-21 fusokine: The tail wags the dog

In this issue of Blood, Bhatt et al have shown that fusing interleukin 21 (IL-21) to an anti-CD20 antibody results in a molecule that has superior antilymphoma activity than each of its individual components.¹ They find that the fused IL-21 induces direct cytotoxicity to the lymphoma cells but also activates immune effector cells that enhance the efficacy of the anti-CD20 antibody. The addition of IL-21 to an anti-CD20 antibody to form an anti-CD20-IL-21 fusokine therefore provides enhanced activity in 2 ways: firstly, it increases cytotoxicity directly targeting the malignant cell, and secondly, it modulates and augments the anti-tumor immune response (see figure).