Immunoreceptor Engineering and Synthetic Cytokine Signaling for Therapeutics

• Published in: Trends in immunology Vol. 40; no. 3; pp. 258 - 272
• Main Authors: Scheller, Jürgen, Engelowski, Erika, Moll, Jens M., Floss, Doreen M.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.2019; Elsevier Limited
• Subjects: Animals; Antibodies; Antigens; Antigens, Neoplasm - immunology; Autoimmunity; B-Lymphocytes - immunology; Binding sites; Biology; Cancer; CAR; Chimeric antigen receptors; Cytokine; Cytokine receptor; Cytokine receptors; Cytokines; Cytokines - genetics; Cytokines - metabolism; Design; FDA approval; Genetic Engineering; Growth hormones; Humans; Immunotherapy; Immunotherapy - trends; Interleukin; Kinases; Ligands; Lymphocytes; Lymphocytes T; Mutation; Neoplasms - immunology; Neoplasms - therapy; Physiology; Proteins; Receptors; Receptors, Chimeric Antigen - genetics; Receptors, Cytokine - genetics; Receptors, Cytokine - metabolism; Signal Transduction; T cell receptors; T-Lymphocytes - immunology; Tumor necrosis factor-TNF; CAR; Interleukin; Immunotherapy; Cytokine; Cytokine receptor
• ISSN: 1471-4906; 1471-4981
• DOI: 10.1016/j.it.2019.01.001

Cytokines control immune-related events and are critically involved in a plethora of physiological and pathophysiological processes including autoimmunity and cancer development. Accordingly, modulation of natural cytokine signaling by antibodies and small molecules has improved therapeutic regimens. Synthetic biology sets out to optimize immunotherapeutics, with chimeric antigen receptor (CAR) T cell immmunotherapy being the first example to combine synthetic biology with genetic engineering during therapy. Hence, synthetic cytokines and cytokine receptors, as well as constitutively active cytokine receptor variants, are emerging as tools to improve or modulate immunotherapeutic strategies. This review focuses on recent developments in the growing field of synthetic cytokine signaling, providing an outlook for developing applications that involve physiological targets of immunotherapy. Synthetic cytokine biology deconstructs and reassembles cytokines and their receptors to design biological devices as therapeutics. Synthetic cytokines, including neoleukins and synthekines, can activate selective or nonnatural receptor combinations and subsequently induce unique signaling patterns. Cytokines coupled to nanoparticles, peptides, or antibodies and fusokines can allow cell-targeted therapies. Naturally occurring and synthetic constitutively active cytokine receptors have been described for all cytokine receptor classes and might improve immunotherapy approaches. Fully synthetic cytokine signaling systems can allow precisely orchestrated cellular responses. They have been shown to modulate immune responses and presumably, might support immunotherapeutics.