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Tumor Necrosis Factor
Published in Jason Kelley, Cytokines of the Lung, 2022
Systemic increases in endogenous TNF also cause pulmonary injury. Endogenous TNF induced by the intraperitoneal injection of LPS in adjuvant-primed mice was shown by Remick et al. (1990) to be associated with increases in pulmonary neutrophils, which were inhibited by anti-TNF serum. In another model of pulmonary injury following endogenous expression of systemic TNF, lung injury occurred in an experimental model of hepatic ischemia and reperfusion (Collette et al., 1990a,b). Pulmonary edema and leukocyte accumulation were again ameliorated with antiserum to TNF (Colletti et al., 1990a,b). Pulmonary injury was also observed accompanying the high circulating levels of TNF induced by in vivo administration of anti-CD3 monoclonal antibody, suggesting that T cell-derived systemic release of TNF can cause the same pulmonary lesions as macrophage-derived TNF (Ferrau et al., 1990).
Extracorporeal Purging of Bone Marrow Grafts by Dye-Sensitized Photoirradiation
Published in Adrian P. Gee, BONE MARROW PROCESSING and PURGING, 2020
MC 540-sensitized photoirradiation at doses comparable to those used for the purging of experimental and clinical bone marrow grafts impairs several lymphocyte functions.60,61 It inhibits the anti-CD3-, phytohemagglutinin-, and concanavalin A-induced proliferation of T cells, mixed lymphocyte cultures, pokeweed mitogen-induced immunoglobulin synthesis, helper activity provided by purified T cells in cocultures containing untreated B cells, and Ig synthesis by B cells in coculture with untreated T cells or after stimulation with Epstein Barr virus. Furthermore, MC 540-sensitized photoirradiation abolishes calcium flux responses of T cells to anti-CD3 monoclonal antibody and the induction of mRNA for interleukin-2, interleukin-2 receptor, interleukin-4, and tumor necrosis factor-α by anti-CD3 monoclonal antibody.60,61
Therapy with lnterleukin-2 and Tumor-Derived Activated Lymphocytes
Published in Ronald H. Goldfarb, Theresa L. Whiteside, Tumor Immunology and Cancer Therapy, 2020
In patients with non-melanoma cancers (summarized in Table 7), metastases from patients with solid tumors were harvested from 196 patients for the purpose of growth TDAC. Cells were prepared from autologous tumor cultures by incubation with rIL-2 followed by repeated exposure to tumor antigen and/or anti-CD3 monoclonal antibody. Initial growth success was achieved in 66%; 45 of 56 (80%) of these early cultures were subsequently expanded for in vivo therapy. It took a mean of 69.4 ± 24.0 days to grow TDAC for treatment. Thirty-eight patients were treated with cyclophosphamide (1 g/m2) on day one followed by a 96-hour continuous infusion of rIL-2 (18 × 106 IU/m2/day) on days 2–5 and approximately 1011 TDAC on day 2. Patients subsequently received monthly rIL-2 as a 96-hour constant infusion if their cancers were stable or regressing. Median age was 51 years; 58% were male. Performance status was 0–1 in 64%, 29% had lung metastases; 34% had liver metastases. Responses were seen only in 1/38 patients (3%); a partial response in a patient with lymphoma. Forty-two percent were stable 90 days post-treatment, the rest were progressive or inevaluable. We conclude that a treatment plan for rIL-2/TDAC is technically difficult, costly, and not practical under these conditions for these tumor types. Clinical results to date are not clearly different than those obtained with other rIL-2 regimens (47).
Non-alcoholic fatty liver disease and intestinal immune status: a narrative review
Published in Scandinavian Journal of Gastroenterology, 2022
Hao Wu, Yalan Lei, Jingwei Mao
Recently published preclinical and clinical data on oral administration of anti-CD3 monoclonal antibody and recombinant anti-TNF-α fusion protein (PRX106) are discussed [61–64]. The anti-CD3 monoclonal antibody is active at mucosal surfaces and it induces expansion of regulatory T cells that suppresses immune disease progress in animal models such as experimental autoimmune encephalitis, diabetes, lupus, arthritis, atherosclerosis and is being tested in humans. Oral anti-CD3 does not enter the bloodstream or modulate CD3 from the cell surface but acts locally in the gut to induce Tregs in the MLNs [65]. In the Phase-IIa trial, oral administration of anti-CD3 MAb to patients with NASH was safe and well-tolerated; in addition, beneficial biological effects were noted in several clinically relevant parameters [64]. The findings provide the basis for future trials to investigate the effect of oral anti-CD3 MAb immunotherapy in patients with NASH. Foralumab is a fully human anti-CD3 mAb that has recently been shown to exert a potent anti-inflammatory effect in humanized mice. It is being developed for the treatment of NASH [61].
Evaluation of Expression of LRBA and CTLA-4 Proteins in Common Variable Immunodeficiency Patients
Published in Immunological Investigations, 2022
Fereshte Salami, Saba Fekrvand, Reza Yazdani, Sepideh Shahkarami, Gholamreza Azizi, Yasser Bagheri, Samaneh Delavari, Sahar Shariati, Seyed Alireza Mahdaviani, Mohammamd Nabavi, Afshin Shirkani, Hassan Abolhassani, Morteza Samadi, Asghar Aghamohammadi
Expression of LRBA and CTLA-4 was assessed using western blotting and flow cytometry, respectively. In the first step, human peripheral blood mononuclear cells (PBMCs) were extracted from whole heparinized blood of newly diagnosed CVID patients and their matched healthy donors using Ficoll-Hypaque gradient separation. PBMCs were cultured in complete RPMI-1640 medium supplemented with 1/100 penicillin-streptomycin (Gibco, USA) at a density of 1 × 106 cells/ml and stimulated with 10 μg/ml of phytohemagglutinin (PHA, Sigma-Aldrich, USA) for the assessment of LRBA for 72 hours at 37°C and 5% carbon. Stimulation with an anti-CD3 monoclonal antibody (mAb, eBioscience, USA) and anti-CD28 mAb (eBioscience) for 72 hours at 37°C and 5% CO2 were performed for the assessment of CTLA-4.
Isolated limb perfusion with melphalan activates interferon-stimulated genes to induce tumor regression in patients with melanoma in-transit metastasis
Published in OncoImmunology, 2020
Junko Johansson, Roberta Kiffin, Ebru Aydin, Malin S. Nilsson, Kristoffer Hellstrand, Per Lindnér, Peter Naredi, Roger Olofsson Bagge, Anna Martner
PBMCs from healthy donors were cultured for 4 days in IMDM with 10% heat-inactivated fetal bovine serum, 100 U/ml penicillin-streptomycin, 10 μg/ml Fungin™, 2 mM L-glutamine, 1 mM sodium pyruvate and 500 U/ml recombinant human IL-2. Half of the cultures were also supplemented with an anti-CD3 monoclonal antibody (clone: OKT3, 50 ng/ml, eBioscience™, #16-0037-85) in order to activate the T cells. After 4 days, the PBMCs were resuspended in IMDM with 0.1% bovine serum albumin (MP Biomedical, #160069) at a concentration of 1 × 106 cells/ml, and 100 μl of the cell suspension was added to Transwell® inserts with pore size 5.0 μm placed in flat-bottomed 24-well plates (Corning® Transwell® polycarbonate membrane cell culture inserts, Sigma-Aldrich, #CLS3421-48EA). IMDM with 10% heat-inactivated fetal bovine serum, with or without recombinant human CXCL10 (100 ng/ml, R&D Systems, #266-IP) as a positive control or supernatants obtained from PBMC-melanoma co-cultures collected 48 h after start of the co-culture (two parts supernatant and one part complete IMDM medium), was added to the wells underneath the Transwell® inserts. After 4 h of incubation at 37°C, the migrated cells were collected, stained with T cell and NK cell markers and counted using counting beads (CountBright™ Absolute Counting Beads, Thermo Fisher Scientific, #C36950) by flow cytometry. The fraction of cells that migrated was calculated as fold change to the negative control, e.g. IMDM with only 10% serum and no additional chemoattractant.