Immunocytokines and cytokine neutralization for cancer immunotherapy.

Abstract

Despite deep and growing knowledge of cytokine functions, immunotherapies based on the control of these molecules have minimally impacted cancer patient management because of limited efficacy and narrow therapeutic windows. Opportunities to enhance efficacy and mitigate side effects arise from local delivery and targeting antitumor cytokines to tumor tissue via chimeric fusion with antibodies (immunocytokines). Conversely, neutralization of protumor cytokines using antibodies, cytokine traps, or receptor antagonists offer the opportunity to increase the efficacy of conventional immunotherapy with checkpoint inhibitors while reducing their side effects. Exploiting the immunobiology of interleukin (IL)-2, IL-12, IL-15, IL-18, and IL-21 in synergistic combinations with other treatments holds promise. The antagonistic neutralization of transforming growth factor-β, tumor necrosis factor, IL-1, IL-6, and CXCR1/2 chemokines and growth differentiation factor 15 also seems to be very convenient, again as part of combination strategies.