Therapeutic synthetic and natural materials for immunoengineering

Abstract

Immunoengineering is a rapidly evolving field that has been driving innovations in manipulating immune system for new treatment tools and methods. The need for materials for immunoengineering applications has gained significant attention in recent years due to the growing demand for effective therapies that can target and regulate the immune system. Biologics and biomaterials are emerging as promising tools for controlling immune responses, and a wide variety of materials, including proteins, polymers, nanoparticles, and hydrogels, are being developed for this purpose. In this review article, we explore the different types of materials used in immunoengineering applications, their properties and design principles, and highlight the latest therapeutic materials advancements. Recent works in adjuvants, vaccines, immune tolerance, immunotherapy, and tissue models for immunoengineering studies are discussed.

Fig. 1

Key components of vaccines are listed as antigens, adjuvants, delivery vehicls, and targeting components, including examples of each. Upon injection, antigen presenting cells (APCs) uptake vaccine components, present the antigen, and prime adaptive immune cells. This process is depicted above. Adapted from “Common Components of Vaccines”, by BioRender.com (2023). Retrieved from https://app.biorender.com/biorender-templates

Fig. 2

Small molecule agonists of many PRRs have been identified, including TLR1/2, TLR4, TLR7/8, STING, and NLRP3. Key examples of these are shown, grouped by protein target, with associated CAS numbers. PRR: pattern recognition receptor; TLR: Toll-like receptors; PRR: pattern recognition receptor; TLR: Toll-like receptor; NLRP3: nucleotide oligomerization domain-like receptor family, pyrin domain containing 3; STING: stimulator of interferon genes.

Fig. 3

Consequences of PEGylation of biologics. When therapeutic proteins are attached to PEG, several key benefits are conferred, including increased hydrophilicity and molecular weight, decreased immunogenicity, and tunable bioactivity. The practical implications of these alterations are graphically depicted.

Fig. 4

Antibody drug conjugates are generally synthesized through three main chemistries, including lysine (amine) to NHS ester, cysteine (thiol) to maleimide, or non-natural amino acid (azide) to strained alkyne (DBCO or BCN). Each of the three chemistries are shown here with a high-level description of their key favorable or unfavorable properties. NHS: N-hydroxysuccinimide; DBCO: dibenzocyclooctyne; BCN: bicyclononyne; DAR: drug-antibody ratio.

Fig. 5

Chemical structures of lipid nanoparticle components. Lipid nanoparticles are generally made of cationic lipids, ionizable lipids, phospholipids, PEGylated lipids, and cholesterol. Key examples in each of these classes are depicted with structures, names, and CAS numbers.

Fig. 6

Important structural features of mRNA. mRNA synthesized via in vitro transcription must recapitulate key structural features of naturally-produced mRNA, such as the 5’ cap structure and nucleoside chemical modifications, in order to reduce the immunogenicity of the mRNA and to improve mRNA translation efficacy and stability. These include analogs to uridine in the 5’ UTR, coding sequence, and 3’ UTR; as well as key analogs for the 5’ cap.

Fig. 7

Comparison of morphology and composition of different nanoparticle technologies, which includes both lipid- and polymer-based micelles, vesicles, and nanoparticles, each of which have unique compositions to favor their unique morphology.