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Recent Advances of Nanotechnologies for Cancer Immunotherapy Treatment
Published in Loutfy H. Madkour, Nanoparticle-Based Drug Delivery in Cancer Treatment, 2022
CD47 is a transmembrane protein, and it could produce integrin-associated protein that transmits “don’t eat me” signal to immune system [221]. By binding to the ligand signal regulatory protein alpha (SIRPα), it can suppress phagocytosis. CD47 is expressed ubiquitously in various kinds of human cells, and increasing evidence has shown that CD47 is overexpressed in a variety of tumor cells. Owing to the CD47/SIRPα interaction, tumor cells could avoid clearance by phagocytic cells resulting in immune evasion [222]. Recently, it is demonstrated that anti-CD47 antibody could turn off “don’t eat me” signal and promote phagocytosis of tumor cells by macrophages. Moreover, it can initiate antitumor immune response [223]. Hence, human anti-CD47 monoclonal antibodies are being evaluated for malignant tumor treatment. Although tumor-associated myeloid cells are thought to be related to metastasis and drug resistance, some of them, such as macrophages and DCs, play an essential role in antigen presentation and subsequent antitumor immunity of cytotoxic T cells. By using antibody KWAR23 to block SIRPα, the antitumor immunity of myeloid cells in human Burkitt’s lymphoma xenograft model could be significantly enhanced by promoting the infiltration of neutrophils and macrophages. It might benefit a number of patients by eliciting durable responses [224]. In addition, CD47 blockade also promoted the phagocytosis of DCs on tumor cells and triggered consequent antitumor immune responses for eliminating immunogenic tumors. It provided combination strategy with chemotherapy against tumor relapse [225].
Recent Advances in Biocompatibility
Published in Yaser Dahman, Biomaterials Science and Technology, 2019
Drug-eluting stents cannot achieve full potential when the patient suffers from diseases such as diabetes, renal dysfunction, or patients with small vessel diameters (Slee et al. 2016). Stents coated with drugs also have a higher occurrence of late stent thrombosis by preventing endothelium re-growth (Slee et al., 2016). However, an alternative stent that improves biocompatibility is still required (Slee et al., 2016). Slee et al. (2016) used CD47 as an alternative coating for stents. CD47 is a transmembrane protein that, when it binds to Signal Regulatory Protein Alpha (SIRP α), provides an anti-inflammatory response. In 2011, Stachelek et al. was able to demonstrate that CD47 modified polymer surfaces reduce inflammation in-vivo and in-vitro (Stachelek et al., 2011; Slee et al., 2016). Another study completed by Finley et al. (2012) demonstrated that CD47 surfaces reduced cell adhesion and platelets and neutrophils activation. Slee et al. (2016), suggest the use of CD47 on the stent’s surface to enhance biocompatibility and prevent early inflammatory events that result in restenosis (Slee et al., 2016). The purpose of this study was to demonstrate an in-vitro CD47 anti-inflammatory capacity and in-vivo CD47 inhibition of ISR in rats (Slee et al., 2016). Figure 2.10 illustrates the design of CD47 stent. The in-vitro anti-inflammatory capacity of CD47 was determined using different steel foil samples by investigating their ability to inhibit macrophage attachment. The results demonstrated that CD47-steel foil samples had a lower macrophage attachment compared to other samples. This suggests that CD47 has the potential to prevent acute inflammation (Slee et al., 2016). The in-vivo efficacies of stents with and without CD47 were investigated using rats. pepCD47 was chosen due to results from Figure 2.11. The stents were placed in the rats’ carotid arteries for 30 minutes, 3 days, and 14 days. After each time period, inflammatory responses (the number of white, red, and platelet cells) and thrombosis were quantified. The SEM results demonstrated that CD47 reduced platelet attachment within 30 minutes (Figure 2.12a) and macrophage recruitment after 3 days (Figure 2.12 b), indicating that CD47 can prevent early acute inflammatory responses, thus having the ability to prevent ISR (Slee et al., 2016).
Development of an immunosuppressive camouflage-coating platform with nanocellulose and cell membrane vesicles
Published in Journal of Biomaterials Science, Polymer Edition, 2020
Akihiro Nishiguchi, Tetsushi Taguchi
Cells protect themselves from attack by immune cells through self-recognition signaling. Macrophages, which are responsible for removal of foreign materials [14], recognize autologous cells and others through signal-regulatory protein-α (SIRP-α) and CD47 signaling. SIRP-α belongs to a family of transmembrane glycoproteins involved in the regulation of leukocyte function [15]. When SIRP-α on the surface of macrophages binds to CD47 on autologous cells, the negative signal transduction attenuates the phagocytic activity of macrophages [16]. This anti-phagocytic signal is called the “don’t eat me signal” that distinguishes healthy self-cells from microbes, dying cells, and other foreign materials; in addition, CD47 functions as a marker of “self.” Moreover, CD47-SIRP-α interaction downregulates inflammatory responses through the immunoreceptor tyrosine-based inhibitory motif (ITIM) sequence that negatively regulates immune responses [17–19]. Interestingly, cancer cells also leverage CD47-SIRP-α signaling by overexpressing CD47 to escape phagocytosis by macrophages for their survival. Inspired by this self-recognition system in the body, we achieved surface modification of synthetic biomaterials with recombinant CD47 proteins or analogous peptides to reduce inflammatory responses against materials [18, 20] and evade immune clearance of nanoparticles for targeting [21]. To further mimic complex cell surface structures, we employed isolated cell membranes as coating materials [22–24]. Cell membrane-derived vesicles (CVs) possess complex cell surface properties and this functionality could be transferred to implant biomaterials. CV coating technology allows camouflaging of implants, thus avoiding rejection by the immune system. It was reported that coating of nanoparticles with CD47-bearing CVs effectively suppressed macrophage uptake [25]. Moreover, this method can allow synergistic effects by a variety of ligands that are stabilized with cell membrane lipids. However, it is difficult to coat CVs onto flat surfaces with low curvature. Therefore, supporting layers such as nanofibers [26] need to be applied for coating of CVs onto implants.