Abstract
A number of cytokines have shown beneficial effects in preclinical animal models of cancer and chronic inflammatory diseases. However, cytokine treatment is often associated with severe side effects, which prevent the administration of clinically relevant doses in humans. Immunocytokines are a novel class of biopharmaceuticals, consisting of a cytokine moiety fused to monoclonal antibodies or to an antibody fragment, which selectively accumulate at the disease site and thereby enhance the therapeutic effects of cytokines. This review surveys the recent preclinical and clinical advances in the field, with a special focus on the impact of antibody formats, target antigen and cytokine moieties on the therapeutic performance in vivo. We also discuss emerging data about the possibility to combine immunocytokines with other pharmacological agents.
Highlights
A number of cytokines have shown beneficial effects in preclinical animal models of cancer and immune disorders and represent promising agents for therapy
Recent findings describe the formation of activating immune synapses (AIS) between FcR-deficient natural killer (NK) cells and tumor cells mediated by interleukin 2 (IL2) immunocytokines
The most promising results were reported for fusion proteins with interleukin 2 (IL2), interleukin 12 (IL12) and tumor necrosis factor (TNF)
Summary
A number of cytokines have shown beneficial effects in preclinical animal models of cancer and immune disorders and represent promising agents for therapy. The most promising results were obtained by intratumoral or peritumoral application of cytokines and gene therapy approaches, including intratumoral implantation of cytokine-producing cells or cytokine gene transfection of cancer cells before implantation [1,2,3,4,5]. These approaches are rarely applicable in the clinical setting and are typically not efficacious in the case of disseminated disease. One way to achieve specific localization of cytokines at the disease site after systemic administration consists in the use of antibodies as delivery vehicles, leading to a new class of biopharmaceutical agents, termed “immunocytokines”. Their therapeutic potency depends on molecular format, target antigen and cytokine fusion, as well as their combinatory function with other pharmacological agents
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