Biological drug and drug delivery-mediated immunotherapy

Abstract

The initiation and development of major inflammatory diseases, i.e., cancer, vascular inflammation, and some autoimmune diseases are closely linked to the immune system. Biologics-based immunotherapy is exerting a critical role against these diseases, whereas the usage of the immunomodulators is always limited by various factors such as susceptibility to digestion by enzymes in vivo, poor penetration across biological barriers, and rapid clearance by the reticuloendothelial system. Drug delivery strategies are potent to promote their delivery. Herein, we reviewed the potential targets for immunotherapy against the major inflammatory diseases, discussed the biologics and drug delivery systems involved in the immunotherapy, particularly highlighted the approved therapy tactics, and finally offer perspectives in this field.

Keywords: AAs, amino acids; ACT, adoptive T cell therapy; AHC, Chlamydia pneumonia; ALL, acute lymphoblastic leukemia; AP, ascorbyl palmitate; APCs, antigen-presenting cells; AS, atherosclerosis; ASIT, antigen-specific immunotherapy; Adoptive cell transfer; ApoA–I, apolipoprotein A–I; ApoB LPs, apolipoprotein-B-containing lipoproteins; Atherosclerosis; BMPR-II, bone morphogenetic protein type II receptor; Biologics; Bregs, regulatory B lymphocytes; CAR, chimeric antigen receptor; CCR9–CCL25, CC receptor 9–CC chemokine ligand 25; CD, Crohn's disease; CETP, cholesterol ester transfer protein; CTLA-4, cytotoxic T-lymphocyte-associated protein-4; CX3CL1, CXXXC-chemokine ligand 1; CXCL 16, CXC-chemokine ligand 16; CXCR 2, CXC-chemokine receptor 2; Cancer immunotherapy; CpG ODNs, CpG oligodeoxynucleotides; DAMPs, danger-associated molecular patterns; DCs, dendritic cells; DDS, drug delivery system; DMARDs, disease-modifying antirheumatic drugs; DMPC, 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine; DSS, dextran sulfate sodium; Dex, dexamethasone; Drug delivery; ECM, extracellular matrix; ECs, endothelial cells; EGFR, epidermal growth factor receptor; EPR, enhanced permeability and retention effect; ET-1, endothelin-1; ETAR, endothelin-1 receptor type A; FAO, fatty acid oxidation; GM-CSF, granulocyte–macrophage colony-stimulating factor; HA, hyaluronic acid; HDL, high density lipoprotein; HER2, human epidermal growth factor-2; IBD, inflammatory bowel diseases; ICOS, inducible co-stimulator; ICP, immune checkpoint; IFN, interferon; IL, interleukin; IT-hydrogel, inflammation-targeting hydrogel; Immune targets; Inflammatory diseases; JAK, Janus kinase; LAG-3, lymphocyte-activation gene 3; LDL, low density lipoprotein; LPS, lipopolysaccharide; LTB4, leukotriene B4; MCP-1, monocyte chemotactic protein-1; MCT, monocrotaline; MDSC, myeloid-derived suppressor cell; MHCs, major histocompatibility complexes; MHPC, 1-myristoyl-2-hydroxy-sn-glycero-phosphocholine; MIF, migration inhibitory factor; MM, multiple myeloma; MMP, matrix metalloproteinase; MOF, metal–organic framework; MPO, myeloperoxidase; MSCs, mesenchymal stem cells; NF-κB, nuclear factor κ-B; NK, natural killer; NPs, nanoparticles; NSAIDs, nonsteroidal anti-inflammatory drugs; PAECs, pulmonary artery endothelial cells; PAH, pulmonary arterial hypertension; PASMCs, pulmonary arterial smooth muscle cells; PBMCs, peripheral blood mononuclear cells; PCSK9, proprotein convertase subtilisin kexin type 9; PD-1, programmed death protein-1; PD-L1, programmed cell death-ligand 1; PLGA, poly lactic-co-glycolic acid; Pulmonary artery hypertension; RA, rheumatoid arthritis; ROS, reactive oxygen species; SHP-2, Src homology 2 domain–containing tyrosine phosphatase 2; SLE, systemic lupus erythematosus; SMCs, smooth muscle cells; Src, sarcoma gene; TCR, T cell receptor; TGF-β, transforming growth factor β; TILs, tumor-infiltrating lymphocytes; TIM-3, T-cell immunoglobulin mucin 3; TLR, Toll-like receptor; TNF, tumor necrosis factor; TRAF6, tumor necrosis factor receptor-associated factor 6; Teff, effector T cell; Th17, T helper 17; Tph, T peripheral helper; Tregs, regulatory T cells; UC, ulcerative colitis; VEC, vascular endothelial cadherin; VEGF, vascular endothelial growth factor; VISTA, V-domain immunoglobulin-containing suppressor of T-cell activation; YCs, yeast-derived microcapsules; bDMARDs, biological DMARDs; hsCRP, high-sensitivity C-reactive protein; mAbs, monoclonal antibodies; mPAP, mean pulmonary artery pressure; nCmP, nanocomposite microparticle; rHDL, recombinant HDL; rhTNFRFc, recombinant human TNF-α receptor II-IgG Fc fusion protein; scFv, single-chain variable fragment; α1D-AR, α1D-adrenergic receptor.

Graphical abstract

Figure 1

Immunotherapy for cancer and the used drug delivery systems (DDSs).

Figure 2

Immunotherapy for rheumatoid arthritis (RA) and the used DDSs.

Figure 3

Immunotherapy for inflammatory bowel diseases (IBD) and the used DDSs.

Figure 4

Immunotherapy for atherosclerosis (AS) and the used DDSs.

Figure 5

Immunotherapy for pulmonary arterial hypertension (PAH) and the used DDSs.