Current Immunotherapy Strategies for Rheumatoid Arthritis: The Immunoengineering and Delivery Systems

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease accompanied by persistent multiarticular synovitis and cartilage degradation. The present clinical treatments are limited to disease-modifying anti-rheumatic drugs (DMARDs) and aims to relieve pain and control the inflammation of RA. Despite considerable advances in the research of RA, the employment of current clinical procedure is enormous, hindered by systemic side effect, frequent administration, tolerance from long-lasting administration, and high costs. Emerging immunoengineering-based strategies, such as multiple immune-active nanotechnologies via mechanism-based immunology approaches, have been developed to improve specific targeting and to reduce adverse reactions for RA treatments. Here, we review recent studies in immunoengineering for the treatment of RA. The prospect of future immunoengineering treatment for RA has also been discussed.

Fig. 1

Biological pathways and risk factors for RA pathological processes.

Fig. 2.

The schematic illustration of immunomodulatory therapy of MSC in treating patients with RA. The mechanism of MSCs treated by different approaches to enhance immunomodulatory and mediate the pathological processes of RA. BAFF, B cell activating factor; APRIL, a proliferation-inducing ligand; EV, extracellular vesicles; IDO, indoleamine 2,3-dioxygenase; ILT, immunoglobulin-like transcript; ICAM-1, intercellular adhesion molecule-1; FLT3L, FMS-like tyrosine kinase-3 ligand; TNFAIP3, tumor necrosis factor–α-induced protein 3.

Fig. 3.

(A) Schematic illustration of immunomodulatory therapy of DCs in patients with RA [36]. (B) Schematic illustration of CAR-T-mediated autoreactive B cell elimination therapy for RA [39].

Fig. 4.

Apart from direct cell therapy, current immunomodulatory strategies could also modify the different kinds of chemicals (e.g., folic acid and dextran) on the surface of the carriers (e.g., nanoparticles, liposome, hydrogel, scaffold, adenovirus, and lentivirus) to improve the affinity to specific targeted cell surface and suppress immune activity in vivo, which might bring a new method for the immunoengineering treatment of RA.

Fig. 5.

The schematic of immunoengineering modified with nanotechnology targeting the active M1 macrophages for RA to play the intracellular anti-inflammatory effect.

Fig. 6.

Schematic illustration for the synthesis of (A) HA hydrogel [81], (B) MTX-GDFDFDY hydrogels [82], and (C) DS-FLs/DEX hydrogels [83], which could exert anti-inflammatory effect by sustaining the release of camptothecin, MTX, and DEX. (D) Schematic illustration showing the fabrication process of self-healing infliximab-based hydrogels combined with 3D printed porous metal scaffolds (3DPMS) to deliver ADSCs in aiding RA management.

Fig. 7.

With the inclusion of anti-inflammatory therapy, the engineering biomaterial therapy, and the anti-cytokine cell therapy, the more specific RA immunoengineering therapy could be invented to offer potential possibilities to RA patient.