Harnessing cytokine immunocomplexes and cytokine fusion proteins for cancer Therapy: Mechanisms and clinical potential

Cytokines are pivotal regulators of cellular functions and immune responses, making them highly promising targets for cancer immunotherapy. Despite their widespread clinical application, the effectiveness of cytokine immunotherapy is often hampered by their pleiotropic effects, short half-lives, uneven biodistribution, and severe side effects at high dosages. Recent advancements in cytokine biology have led to the development of cytokine-antibody immunocomplexes and cytokine fusion proteins, offering a new paradigm in cancer treatments. These innovations foster the ability of cytokines to selectively activate specific cancer-targeting immune cell populations, such as CD8 T cells and NK cells, effectively inhibiting tumour progression. Furthermore, both therapeutic approaches can mitigate systemic toxicities and prolong the biological activity of cytokines in the body. This review delves into the recent advancements of cytokine immunocomplexes and cytokine fusion proteins, with a particular focus on interleukin-2 (IL-2), IL-7 and IL-15, which are in clinical/preclinical development. Moreover, we discuss the therapeutic benefits of these approaches observed in recent preclinical and clinical studies, along with the challenges that must be addressed to fully unlock their potential in cancer immunotherapy.