Engineered Cytokines for Cancer and Autoimmune Disease Immunotherapy

• Type of Material: Article
• Authors: Biaggio Uricoli, Georgia Institute of Technology; Lacey A Birnbaum, Georgia Institute of Technology; Priscilla Do, Georgia Institute of Technology; James M Kelvin, Georgia Institute of Technology; Juhi Jain, Emory University; Emma Costanza, Georgia Institute of Technology; Andrew Chyong, Georgia Institute of Technology; Christopher Porter, Emory University; Sarwish Rafiq, Emory University; Erik Dreaden, Emory University
• Language: English
• Date: 2021-03-09
• Publisher: WILEY
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2021 Wiley‐VCH GmbH
• Final Published Version (URL): http://dx.doi.org/10.1002/adhm.202002214
• Title of Journal or Parent Work: ADVANCED HEALTHCARE MATERIALS
• Volume: 10
• Issue: 15
• Start Page: e2002214
• End Page: e2002214
• Grant/Funding Information: This work was supported in part by the St. Baldrick’s Foundation (Research Grant 641261), the US Department of Defense (Idea Award CA180783), the AAI Careers in Immunology Fellowship Program, the National Institutes of Health Research Training Program in Immunoengineering (T32EB021962), the American Cancer Society (IRG-17-181-05), the Donaldson Charitable Trust (Research Synergy Fund), the Winship Cancer Institute of Emory University, the Aflac Cancer and Blood Disorders Center at Children’s Healthcare of Atlanta, and the Wallace H. Coulter Department of Biomedical Engineering at Emory University and the Georgia Institute of Technology. The content here is solely the responsibility of the authors and does not necessarily represent the official views of the organizations acknowledged herein.
• Keywords: RHEUMATOID-ARTHRITIS; Materials Science; Materials Science, Biomaterials; INTERFERON-GAMMA; Engineering, Biomedical; RANDOMIZED PHASE-II; HIGH-DOSE INTERLEUKIN-2; immunotherapy; RECOMBINANT HUMAN INTERLEUKIN-10; T-CELL THERAPY; Engineering; APOPTOSIS-INDUCING LIGAND; drug delivery; Nanoscience & Nanotechnology; Science & Technology; drug design; immune cell signaling; Science & Technology - Other Topics; CHIMERIC ANTIGEN RECEPTOR; Technology; CHRONIC HEPATITIS-C; TUMOR-TARGETING PROPERTIES

Abstract

Cytokine signaling is critical to a range of biological processes including cell development, tissue repair, aging, and immunity. In addition to acting as key signal mediators of the immune system, cytokines can also serve as potent immunotherapies with more than 20 recombinant products currently Food and Drug Administration (FDA)-approved to treat conditions including hepatitis, multiple sclerosis, arthritis, and various cancers. Yet despite their biological importance and clinical utility, cytokine immunotherapies suffer from intrinsic challenges that limit their therapeutic potential including poor circulation, systemic toxicity, and low tissue- or cell-specificity. In the past decade in particular, methods have been devised to engineer cytokines in order to overcome such challenges and here, the myriad strategies are reviewed that may be employed in order to improve the therapeutic potential of cytokine and chemokine immunotherapies with applications in cancer and autoimmune disease therapy, as well as tissue engineering and regenerative medicine. For clarity, these strategies are collected and presented as they vary across size scales, ranging from single amino acid substitutions, to larger protein-polymer conjugates, nano/micrometer-scale particles, and macroscale implants. Together, this work aims to provide readers with a timely view of the field of cytokine engineering with an emphasis on early-stage therapeutic approaches.