Advances in engineering and delivery strategies for cytokine immunotherapy

ABSTRACT

Introduction

Cytokine immunotherapy is a growing field for the treatment of cancer, infectious disease, autoimmunity, and other ailments. Therapeutic cytokines are a class of secreted, small proteins that play a pivotal role in regulating the innate and adaptive immune system by provoking or mitigating immune responses. In the clinic, cytokines are frequently combined with other treatments, such as small molecules and monoclonal antibodies. However, the clinical translation of cytokine therapies is hindered by their short half-life, pleiotropic nature, and off-target effects, which cause diminished efficacy and severe systemic toxicity. Such toxicity limits dosage, thus resulting in suboptimal doses. Accordingly, numerous efforts have been devoted to exploring strategies to promote cytokine therapies by improving their tissue specificity and pharmacokinetics.

Areas covered

Preclinical and clinical research into bioengineering and delivery strategies for cytokines, consisting of bioconjugation, fusion proteins, nanoparticles, and scaffold-based systems.

Expert opinion

These approaches pave the way for the development of next-generation cytokine treatments with greater clinical benefit and reduced toxicity, circumventing such issues currently associated with cytokine therapy.

KEYWORDS:

• cytokine
• fusion protein
• nanoparticle
• hydrogel
• immunotherapy
• microsphere
• RNA

Article highlights

• Cytokine immunotherapy holds great potential in revolutionizing current treatments against various diseases, including cancers, autoimmune diseases, and infectious diseases.

• Bioengineering strategies, such as PEGylation and fusion proteins, can increase circulation time and tissue-targeting ability of cytokines while minimizing unwanted immunogenicity.

• Nanoparticles can be made from an almost limitless number of materials and formulation methods, allowing for the optimization of cytokine treatment.

• Scaffold-based delivery methods, such as microspheres and gels, allow for sustained release, as well as multi-loading of multiple different cytokine cargos.

Acknowledgments

Y Dong acknowledges the support from the Maximizing Investigators’ Research Award R35GM144117 from the National Institute of General Medical Sciences as well as funding from the Icahn School of Medicine at Mount Sinai.

Declaration of interest

Y Dong is a scientific advisory board member of Oncorus Inc, Arbor Biotechnologies, and FL85. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.