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Role of Nanoparticles in Cancer Immunotherapy
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
Immune T cells recognize the antigens shown by MHC class I molecules present on the surface of cancer cells. Downregulating the antigen processing machinery is one of the fundamental mechanisms by which tumor cells evade immune responses. They downregulate major MHC I pathway, proteosome subunits latent membrane protein (LMP)2 and LMP7, transporter associated with antigen processing protein, and tapasin [25–27]. Kumar et al. have shown that some tumor lines do not respond to checkpoint blockade therapy, as they are deficient in MHC class I molecules. For examples, some sublines of B16 (murine melanoma cancer cell line) evade immune responses by downregulating MHC class I molecules from their surfaces [28]. The downregulation of antigen presentation machinery causes reduced tumor antigen that leads to enhanced tumor incidence and metastasis.
Development of Oligonucleotide Delivery, (siRNAs), and (miRNA) Systems for Anticancer Therapeutic Strategy Immunotherapy
Published in Loutfy H. Madkour, Nanoparticle-Based Drug Delivery in Cancer Treatment, 2022
As mentioned above [27], the MHC-I molecule binds the peptide derived from a protein antigen and presents it to T cells. However, we now know that a new paradigm exists for antigen presentation, which is the recognition of nonpeptide antigens, lipid-based antigens that are present on CD1 molecules by T cells or NKT cells [66]. A recent study also revealed that MHC-I molecules presented lipopeptide antigens in addition to peptide antigens [67]. The expression of CD1 was different between human and muroid rodents. The human CD1 family is composed of CD1a, CD1b, CD1c, CD1d, and CD1e, whereas only CD1d is expressed by muroid rodents [68]. These CD1 molecules, which are prominently expressed in APCs, bind lipids such as fatty acids, glycolipids, and lipopeptides. The lipid antigens would be expected to function as a new vaccine against bacterial infections because lipid antigens are mainly found in bacteria, particularly mycobacteria, and induce lipid antigen–specific T cell responses. However, it has been difficult to develop and utilize them as vaccines or tools because of their poor solubility in water. We hypothesized that the lipid antigens would be excellent with LNPs and that a lipid antigen could be incorporated into octaarginine (R8)-modified nanoparticles (R8-NP). R8-NP has a high affinity for cells, efficiently delivers antigens to APCs, and is a potent vaccine carrier [69–71]. It has been recently reported that R8-NP was a potent carrier for lipid antigens [72–78].
Enzymes for Prodrug-Activation in Cancer Therapy
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
The concept of CAR goes back to Gross et al. (1989) who constructed the first chimeric T cell receptor gene, demonstrating the principle of genetically redirecting cytotoxic T cells to tumor cells. This cTCR was expressed on the surface of cytotoxic T lymphocytes, recognized tumor-associated surface antigens and triggered T-cell activation independent of the expression of the antigen peptides-loaded major histocompatibility complex (MHC) molecules (cell surface proteins essential for the immune system to recognize foreign molecules) as required in case of the T cell receptors (TCRs) that recognize antigens in the context of MHC. The MHC is a set of cell surface proteins that in connection with the adaptive immune system binds pathogen-derived antigens to present them on the cell surface for T-cell recognition. An engineering of blood T lymphocytes with a recombinant T-cell receptor of defined specificity can recognize related MHCs of a tumor-associated antigen (TAA). Such genetically engineered T cells have been reported to mediate cancer regression in human patients with metastatic melanoma; tumor recognition was conferred by a T-cell receptor encoding retrovirus (Morgan et al., 2006).
A mathematical model of cytotoxic and helper T cell interactions in a tumour microenvironment
Published in Letters in Biomathematics, 2018
Heidi Dritschel, Sarah L. Waters, Andreas Roller, Helen M. Byrne
There are two populations of T cells, helper and cytotoxic, which are distinguished by their expression of CD4 and CD8 proteins, respectively. Naive helper T cells are activated by antigen presented with a major histocompatibility complex (MHC) class II molecule. (A glossary of the terminology used in this article is provided in Appendix 1.) Naive cytotoxic T cells are activated by antigen presented with an MHC class I molecule. Once activated the helper and cytotoxic T cells perform complementary functions to eliminate the tumour. Helper T cells further differentiate into subpopulations classified by the specific cytokines that they produce. In this way, they regulate multiple aspects of an immune response. For example, they promote the proliferation of cytotoxic T cells, they recruit and promote cells of the innate immune response, and they control levels of inflammation at the tumour site (Hung et al., 1998; Magombedze et al., 2013). (In this work, we do not distinguish these subpopulations.) Cytotoxic T cells scan the body for transformed cells (cancer cells) to which they bind before inducing cell killing.
Genetic variants affecting chemical mediated skin immunotoxicity
Published in Journal of Toxicology and Environmental Health, Part B, 2022
Isisdoris Rodrigues de Souza, Patrícia Savio de Araujo-Souza, Daniela Morais Leme
The MHC molecules are cell surface glycoproteins whose function is to present peptide antigens to T cells. T cell activation may elicit different types of immune reactions, playing an essential role in pathogenesis of infectious and allergic diseases (Orentas et al. 1990; Posadas and Pichler 2007). The human genes encoding MHC molecules such as human leukocyte antigen and HLA are located in a region that spans approximately 3.6 Mb on 6p21.3, and includes not only classical HLA class I (HLA-A, HLA-B and HLA-C) and II genes (HLA-DRA1, HLA-DRB1, HLA-DPA1, HLA-DPB1, HLA-DQA1 and HLA-DQB1) but also a large number of highly polymorphic genes, encoding proteins with immune-related functions, such as TNF (Alfirevic and Pirmohamed 2011).
Immunological response of polysaccharide nanogel-incorporating PEG hydrogels in an in vivo diabetic model
Published in Journal of Biomaterials Science, Polymer Edition, 2022
Tugba Bal, Ismail Can Karaoglu, Fusun Sevval Murat, Esra Yalcin, Yoshihiro Sasaki, Kazunari Akiyoshi, Seda Kizilel
In recent years, rising advances in nano- and biotechnology have led to numerous developments in tissue engineering strategies. One of those strategies is cell-based therapy which aims to repair damaged organs or tissues by injecting, grafting, or implanting viable cells to the patient. Numerous cell types can be employed for cell therapy such as embryonic stem cells (ESC) [1], mesenchymal stem cells (MSC) [2], hematopoietic stem cells (HSC) [3], induced pluripotent stem cells (iPSC) [4]. By using these cell types, various complications can be targeted such as vascular [5], neurological [6], autoimmune [7], and ophthalmologic diseases [8]. However, immune rejection is still one of the most challenging issues for cell-based therapy. Transplanted cells are rejected by the immune system because of genetic mismatch of the major histocompatibility complex (MHC), followed by the T cell activation of the recipient [9]. Researchers have proposed several possible approaches to circumvent transplant rejection: (i) biological and (ii) material approach. The biological approach suggests various strategies like either activation or repression of a specific gene via the CRISPR system [10], localization of the gene of interest inside the target cell through plasmid [11], or adoption of co-culturing with endothelial cells for the vascularization [12]. For instance, Oran et al. showed stellate cells can be engineered to produce chemokine-ligand-22 (CCL22) for regulatory T cell (Treg) recruitment and graft tolerance [11]. On the other hand, the material approach considers the use of synthetic or hybrid materials [13], functionalization of the polymer materials with a ligand for immune privilege or promotion of angiogenesis [12] and synthesis of the polymers as a physical barrier for the prevention of communication of the transplanted cells with the immune cells [14]. Bose et al. made a silicone reservoir that is retrievable and has a porous polymeric membrane to protect encapsulated cells from the immune system by creating a physical barrier between them [14]. In another study, Headen et al. functionalized the surface of PEG microgels by apoptotic form of Fas ligand (FasL) to achieve local immunomodulation [15]. Apart from these examples, multilayer coating of transplanted cells within nano-scale structures would be a promising approach for protection of the graft from the attack of immune cells [16].