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Orders Norzivirales and Timlovirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
By exhaustive investigation on the mechanisms by which Th cells promote CD8+ T-cell responses, the Qβ VLPs were used to display interleukin-15 by chemical coupling and to induce the corresponding antibodies in mice (Wiesel et al. 2010). The Qβ VLPs displaying the cytokines IL-1α and IL-1β were used to neutralize the endogenous cytokines in mice by the evaluation of how oxidative stress and metabolic danger signals converge and mutually perpetuate the chronic vascular inflammation that drives atherosclerosis (Freigang et al. 2011).
Immunomodulatory Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
A recombinant form of IL-2 (aldesleukin, Proleukin™) is the only interleukin approved for cancer therapy and is licensed to treat metastatic renal cell carcinoma. However, the response rate is less than 50%, and it causes capillary leakage leading to hypotension and pulmonary edema which limits its use. Interleukin-1 (IL-1) has also been shown to possess both direct and indirect antitumor effects, and has been investigated for its ability to protect bone marrow cells from the deleterious effects of radiation and chemotherapy. Studies are also underway to determine whether IL-2 can enhance the efficacy of cancer vaccines. Since the recombinant cytokine first became available for clinical use, treatment with IL-2 has been evaluated in many different dose ranges, schedules, and routes of administration in attempts to maximize efficacy and minimize toxicity. While only the high-dose IL-2 IV bolus regimen is approved by the FDA, positive results have been seen in clinical trials that administered this agent by continuous intravenous infusion (CIV) at lower doses for up to 90 days. IL-2 is still important in cancer immunotherapeutic trials and, at the time of writing, there are over 70 clinical trials investigating IL-2 as an agent to stimulate and expand T cells or NK cells.
Host-Directed and Immune-Based Therapies for Human Immunodeficiency Virus Infection
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
Hernan Valdez, Michael M. Lederman, Bharat Ramratnam, Timothy P. Flanigan
Interleukin 15 Interleukin 15 is produced by macrophages, fibroblasts, and epitehelial cells, but not T cells [107]. It has a secondary structure similar to that of IL-2 and shares with that cytokine the ability to enhance T cell proliferation, increase NK cytotoxicity, act as a T cell chemoattractant, and up-regulate the production of TNF-α, γ-interferon, and GM-CSF [108]. Interleukin 15 is synergistic with IL-2 in assays of lymphocyte proliferation [109], Whereas both IL-2 and IL-15 induce lymphocyte proliferation in the context of T cell receptor activation, IL-2 induces it in the absence of T cell receptor engagement and can directly induce HIV-l replication from latently infected cells. Rarely IL-15 induces HIV-l replication [110]. Although no clinical trials with IL-15 in HIV disease have been con ducted, it is expected that this cytokine may correct defective lymphocyte proliferation without increasing the circulating CD4 lymphocyte count. Potential toxicities of IL-15 include vascular leak syndrome [111].
Stevens-Johnson syndrome and toxic epidermal necrolysis: risk factors, causality assessment and potential prevention strategies
Published in Expert Review of Clinical Immunology, 2020
Chu-Chi Lin, Chun-Bing Chen, Chuang-Wei Wang, Shuen-Iu Hung, Wen-Hung Chung
TNF-α is a pro-inflammatory cytokine and has multiple functions in immune response by regulating cell apoptosis, activation, differentiation, and inflammation [99]. Interferon (IFN)-γ, mainly produced by Th1-CD4 + T helper cells, CD8+ CTL, and NK cells, is well known to play an important role in both innate and adaptive immunity against viral and bacterial infection. In the past several decades, IFN-γ had been elucidated in increasing in the skin tissue, blister cells, and plasma of SCARs [100]. Interleukin-15 (IL-15) is responsible for the activation and proliferation of T and NK cells. The survival signals of memory T cell are also provided by IL-15 when in the absence of antigen [101]. Our previous study showed IL-15 as a key cytokine that can increase the cytotoxicity of NK cells and blister cells of SJS/TEN and was associated with the severity and mortality of SJS/TEN patients [102]. In addition to IL-15, other cytokines, chemokines, and chemokine receptors, including IL-2, IL-6, IL-8/CXCL8, IL-10, IL-12, IL-18, CCR3, CXCR3, CXCR4, and CCR10 expressed locally or systemically, have been found to be involved in trafficking, activation, and proliferation of specific subtype T lymphocytes and other leukocytes in SJS/TEN [103].
Virotherapy: Current Trends and Future Prospects for Treatment of Colon and Rectal Malignancies
Published in Cancer Investigation, 2019
Chin Liang Lee, Sanggeetha Veeramani, Aidin Molouki, Swee Hua Erin Lim, Warren Thomas, Suet Lin Chia, Khatijah Yusoff
Adenovirus expression systems have also been considered as vehicles for modifying immune responses to tumour cells, so enhancing the hosts own anti-tumour inflammatory response. One approach to be considered is to increase the expression of an immune-stimulatory gene in tumour cells in order to promote tumour destruction by host inflammatory cells. Interleukin-15 (IL-15) induces T-cell activity and promotes the release of cytokines such as IFN-γ and TNF-α. IL-15 also enhances cytokine receptor expression making cells more sensitive to secreted cytokines. The IL15 gene was inserted into the E3 region of an adenovirus to construct the AdE2F/IL15 recombinant virus [28]. When AdE2F/IL15 was administered to CRC cells in vitro simultaneously with cytotoxic T lymphocytes (CTL)s, synergistic effects on tumour cell antagonism were observed [28]. In a mouse model, tumour growth was inhibited when intra-tumoral injections of AdE2F/IL15 were combined with intravenous CTL administration without observable adverse effects to the mice [28].
Scalable, cGMP-compatible purification of extracellular vesicles carrying bioactive human heterodimeric IL-15/lactadherin complexes
Published in Journal of Extracellular Vesicles, 2018
Dionysios C. Watson, Bryant C. Yung, Cristina Bergamaschi, Bhabadeb Chowdhury, Jenifer Bear, Dimitris Stellas, Aizea Morales-Kastresana, Jennifer C. Jones, Barbara K. Felber, Xiaoyuan Chen, George N. Pavlakis
Small extracellular vesicles (EV) comprise a diverse class of nanosized particles (30–200 nm) produced by cells throughout the body, and include exosomes and microvesicles [1]. Not only do EV play an important role in facilitating intercellular communication in homeostasis, but they also affect immunological pathways [2], cancer progression [3] and treatment response [4]. The functional characteristics of EV lend themselves to diverse clinical applications including diagnostics, prognostics and therapeutics. Immunomodulation using natural or engineered EV, especially for the treatment of cancer, is being explored by multiple groups [5]. Notably, several clinical trials have tested primary human dendritic cell-derived EV as a cell-free cancer vaccine platform [6,7]. One of the immunostimulatory effects associated with dendritic cell EV was direct activation of NK cells through NKG2D and interleukin-15 (IL-15) pathways [8].