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. 2023 Feb;1(2):107-124.
doi: 10.1038/s44222-022-00016-2. Epub 2023 Jan 30.

Targeted modulation of immune cells and tissues using engineered biomaterials

Parisa Yousefpour  1 , Kaiyuan Ni  1 , Darrell J Irvine  1   2   3   4   5
Affiliations

Targeted modulation of immune cells and tissues using engineered biomaterials

Parisa Yousefpour et al. Nat Rev Bioeng. 2023 Feb.

Abstract

Therapies modulating the immune system offer the prospect of treating a wide range of conditions including infectious diseases, cancer and autoimmunity. Biomaterials can promote specific targeting of immune cell subsets in peripheral or lymphoid tissues and modulate the dosage, timing and location of stimulation, thereby improving safety and efficacy of vaccines and immunotherapies. Here we review recent advances in biomaterials-based strategies, focusing on targeting of lymphoid tissues, circulating leukocytes, tissue-resident immune cells and immune cells at disease sites. These approaches can improve the potency and efficacy of immunotherapies by promoting immunity or tolerance against different diseases.

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Figures

Figure 1 |
Figure 1 |. Primary and secondary lymphoid organs.
a | Anatomic distribution of primary and secondary lymphoid organs. NALT, nasal-associated lymphoid tissue; GALT, gut-associated lymphoid tissue. b | General organization of secondary lymphoid organs and sites of key interactions leading to adaptive immunity, using the lymph node (LN) as an example. Shown are orchestrated steps in the early activation of adaptive immune response in response to an antigen (orange): (1a) dendritic cells (DCs, light purple) acquire antigens trafficked into the LN or migrate to the LN from peripheral tissues carrying antigens, which they then present to naïve T cells (blue) to drive T cell activation and proliferation. (1b) B cells (orange) bind to antigens arriving in follicles, triggering initial B cell activation and proliferation. (2) Early-activated B cells receive help signals from CD4+ T cells at the T zone-follicle border, providing signals to drive entry into germinal centres. (3) Activated B cells enter germinal centres where they undergo proliferation and somatic hypermutation to affinity mature their antibody receptor through interactions with follicular helper T cells and the antigens captured on the dendrites of follicular dendritic cells (FDCs).
Figure 2 |
Figure 2 |. Targeting therapeutics to tissue-draining lymph nodes.
a | Passive targeting of lymphatics through particle size. Particles < 5 nm in diam. are preferentially cleared into the blood vasculature, while particles > 50 nm in diam. tend to become trapped in the tissue. Intermediate sized particles (5–50 nm diam.) exhibit preferential trafficking into lymphatic vessels. ECM, extracellular matrix. b | Targeting migratory leukocytes to traffic vaccines and therapeutics to draining lymph nodes. Shown are examples of injectable or implantable biomaterials that attract monocytes or dendritic cells from the local tissue and peripheral blood. The cells are then stimulated by the implanted material, triggering activation and differentiation into migratory antigen presenting cells that carry antigens or other compounds to the draining lymph nodes.
Figure 3 |
Figure 3 |. Targeting lymph node-resident cells and lymph node subregions.
a | Promoting therapeutic entry into lymph nodes (LNs) through depletion of subcapsular sinus (SCS) macrophages. Vaccine adjuvants (red) induce rapid death of SCS macrophages, leading to enhanced entry of antigens and other compounds (orange) into LNs. b | Polymer nanoparticles (blue) efficiently traffic into lymphatic vessels (20–30 nm) but are too large to penetrate the LN paracortex. They chemically release small molecule payloads (red) that rapidly permeate throughout the node. c | Soluble polymers and polymer nanoparticles (NPs) conjugated with ligands for receptors expressed by specific target cell types (such as dendritic cells (DCs)), are taken up by antigen presenting cells (APCs) in LNs and co-deliver vaccine antigens or DC activating compounds. d | (1) NPs activate complement, (2) are captured by SCS macrophages (3) and transferred to non-antigen-specific B cells through complement receptors. (4) These NPs are then transferred to follicular dendritic cells (FDCs), which express high levels of complement and (fragment crystallisable) Fc receptors. e | (1) Ligands for chimeric antigen receptor (CAR) T cells linked to albumin-binding poly(ethylene glycol) (PEG)-lipid moieties traffic from an injection site and bind to endogenous albumin. These compounds are then transferred to LNs (2) where they are inserted into the plasma membrane of macrophages and DCs. Subsequent encounter of CAR T cells with the ligand displayed on the surface of DCs will lead to CAR T cell tandem stimulation by natural costimulatory receptors and cytokine signals provided by the ligand-decorated DCs.
Figure 4 |
Figure 4 |. Targeting systemic lymphoid organs.
Nanoparticle (NP) carriers can target lymphoid organs systemically, including lymph nodes, spleen, bone marrow and tolerogenic antigen presenting cells in the liver. For example, Apolipoprotein-based lipid nanodiscs a preferentially taken up by myeloid cells in the liver, spleen, and bone marrow. Stabilin-funcitonalized nanoparticles are efficiently scavenged by endothelial cells in the liver. Anionic LNPs target antigen presenting cells in the liver, spleen, lymph nodes, and bone marrow.
Figure 5 |
Figure 5 |. Targeting circulating and tissue-resident immune cells.
a | “Backpacking” cells by attaching drug-releasing materials to cells ex vivo prior to adoptive transfer. IL-15 SA, interleukin-15 super agonist; PLGA, poly(lactide-co-glycolide); IFN, interferon. b | Nanoparticles (NPs) functionalized with targeting moieties can bind to circulating immune cells in the blood, which then traffic into different tissues sites with the drug carrier. cRGD, cyclic arginine-glycine-aspartic acid. c | T cell-targeted NPs deliver nucleic acid payloads (DNA or RNA) to circulating lymphocytes, resulting in the expression of chimeric antigen receptors (CARs) and other immunomodulatory gene payloads in situ. d | Albumin is used as a chaperone to transport vaccines across the epithelial barrier in the nasal and respiratory pathways through the neonatal fragment crystallisable (FcRn) receptor. NPs functionalized with hyaluronic acid are phagocytosed by macrophages and other myeloid cells at sites of intestinal inflammation in the gut. e | Systemically-injected NPs passively accumulate in tumours through the enhanced permeation and retention (EPR) effect, or functionalized NPs actively target cells such as programmed death-1 (PD-1+) lymphocytes. Alternatively, biomaterials can be directly injected into tumours to locally present or release immunostimulatory agents in the tumour microenvironment, or promote gene delivery to tumour cells for localized expression of immunomodulatory factors. f | NPs can be modified with targeting moieties or opsonization-triggering components to bind to the endothelial cells of HEVs of the inflamed draining lymph nodes or target different innate immune cells that home to sites of inflammation. cRGD, cyclic arginine-glycine-aspartic acid; HDL, high-density lipoprotein; HEV, high endothelial venules; PNAd, Peripheral lymph node addressin.
Figure 6.
Figure 6.
Targeting tissue-resident immune cells.
See this image and copyright information in PMC

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References

    1. Urquhart L Top companies and drugs by sales in 2021. Nat Rev Drug Discov 21, 251–251 (2022). - PubMed
    1. Dougan M, Luoma AM, Dougan SK & Wucherpfennig KW Understanding and treating the inflammatory adverse events of cancer immunotherapy. Cell (2021) doi:10.1016/j.cell.2021.02.011. - DOI - PMC - PubMed
    1. Seung E et al. A trispecific antibody targeting HER2 and T cells inhibits breast cancer growth via CD4 cells. Nature 603, 328–334 (2022). - PubMed
    1. Muik A et al. Preclinical Characterization and Phase I Trial Results of a Bispecific Antibody Targeting PD-L1 and 4–1BB (GEN1046) in Patients with Advanced Refractory Solid TumorsGEN1046, a Bispecific Antibody Targeting PD-L1 and 4–1BB. Cancer Discov 12, 1248–1265 (2022). - PMC - PubMed
    1. Neri D Antibody-Cytokine Fusions: Versatile Products for the Modulation of Anticancer Immunity. Cancer Immunology Research 7, 348–354 (2019). - PMC - PubMed

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