The T cell activating properties and antitumour activity of Staphylococcal Enterotoxin-like Q

AbstractStaphylococcal enterotoxins (SEs), as typical superantigens, exhibit promising antitumour activity in the clinic, but their unavoidable side effects related to fever and emesis seriously limit their application for the treatment of malignant tumours. Fortunately, the identification of Staphylococcal enterotoxin-like toxins (SEls), which possess amino acid sequences similar to those of classical SEs but exhibit no or low emetic activity, has provided a set of potential immunomodulatory candidates for cancer therapy. The aim of this study was to examine the effect of SElQ on lymphocyte activation and to further demonstrate its antitumour activity both in vitro and in vivo. High-purity SElQ was successfully harvested, and in vitro results confirmed that SElQ can significantly activate mouse- and human-derived lymphocytes in a dose-dependent manner, particularly CD4+ and CD8+ T cells, which showed significant increases in both percentage and absolute number. Further examination revealed that in addition to the originally recognized TCR Vβ5 and 21, TCR Vβ14, 17 and 18 were activated in SElQ-induced human PBMCs. Moreover, the expression of IL-2 and IFN-γ was significantly upregulated in vitro and in vivo after SElQ treatment. Based on the findings that SElQ induces lymphocyte activation and cytokine release, we then confirmed its antitumour activi ty both in vitro and in vivo. The data showed that treatment with a low concentration of SElQ (30 µg/...
Source: Medical Microbiology and Immunology - Category: Microbiology Source Type: research

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Abstract Immune checkpoint inhibitors have revolutionized cancer therapy by blocking inhibitory pathways of the immune system to fight cancer cells. Their use is often limited by the development of autoimmune toxicities, which can affect multiple organ systems and are referred to as immune-related adverse events (irAE). Amongst these are rheumatologic irAE, including inflammatory arthritis, myositis, vasculitis, and others. Rheumatologic irAE seem to be different from irAE in other organs and from traditional autoimmune diseases in that they can occur early or have delayed onset, and can persist chronically, even ...
Source: J Rheumatol - Category: Rheumatology Authors: Tags: J Rheumatol Source Type: research
Publication date: Available online 11 July 2019Source: American Journal of Kidney DiseasesAuthor(s): Roman Shingarev, Ilya G. GlezermanImmunologic control of malignancy has long been recognized as an important determinant of disease progression. Recent advances in immunology have led to the focus on several mechanisms that can be targeted to achieve tumor suppression. In particular, checkpoint inhibition has evolved in less than a decade to become one of the most important strategies in cancer therapy, with a meaningful improvement in patient survival. Six agents have been approved for clinical use to date and many more ar...
Source: American Journal of Kidney Diseases - Category: Urology & Nephrology Source Type: research
Metastatic melanoma treatment has dramatically changed in the last few years, having a breakthrough with the introduction of targeted agents and immunotherapy. PD-1/PD-L1 pathway is one of the physiologic mechanisms of peripheral immune tolerance, but it also represents a mechanism of tumor immune escape. PD-1/PD-L1 inhibitors represent new immune-checkpoint drugs currently used in metastatic melanoma treatment. Resistance to PD-1/PD-L1 axis blockade, which is the main cause of therapeutic failure during therapeutic use of these drugs, could be linked to several mechanism of immune escape. In fact, other inhibitory recepto...
Source: Current Cancer Therapy Reviews - Category: Cancer & Oncology Source Type: research
Publication date: September 2019Source: Biomedicine &Pharmacotherapy, Volume 117Author(s): Li Wang, Deze Zhao, Kang Qin, Faisal UL Rehman, Xiaochun ZhangAbstractIn recent years, immunotherapy has become an innovative technology for cancer therapy with the discovery of immunological checkpoints. It has shown great potential in a variety of advanced cancer treatments. Particularly, significant progress has been achieved in the understanding of programmed death-1/programmed death ligand-1 (PD-1/ PD-L1) pathway. Nivolumab, a human immunoglobulin (Ig)G4 PD-1 monoclonal antibody, was the first PD-1 inhibitor approved in the ...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
The gastric cancer is the second most malignant tumor in the world. HER-2 is one of the key targets for the gastric cancer therapy. Anti-HER-2 antibodies like trastuzumab, exhibits the satisfactory therapeutic...
Source: Journal of Nanobiotechnology - Category: Nanotechnology Authors: Tags: Research Source Type: research
AbstractPurpose of ReviewIn the rapidly developing field of adoptive cell immunotherapy, there is urgent need for discoveries that would improve outcomes, extend the applicability, and reduce the costs. Induced pluripotent stem cells (iPSC) can be a source of broadly applicable cellular immunotherapeutics, which have been manufactured, validated, and banked in advance, and can be applied across HLA barriers. Here, we discuss the recent advances and challenges in the generation of iPSC-derived cellular products for cancer therapy.Recent FindingsiPSCs can be differentiated to functional tumor-specific T and NK cells in vitro...
Source: Current Hematologic Malignancy Reports - Category: Hematology Source Type: research
Summary: The homeostasis of gut microbiome is linked with the balance of host immune system. Increasing evidence showed that cancer therapy would perturb the host immune response and result dysbiosis of immune system, which influenced the efficiency of the therapy. The gut microbes play increasingly significant role in the cancer therapy with the deepening of the research, which modulate the drug efficacy, abolish the anti-cancer effect, and mediate the toxicity. The systems biology provides an opportunity to discover of the important role the gut microbiota playing in almost all aspects of human health. The existed evide...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
CONCLUSION: With the development of promising therapies to boost the innate immune response, there is significant potential for the expansion of the role of immunotherapy as an adjuvant to surgical treatment in colorectal cancer. PMID: 31216061 [PubMed - as supplied by publisher]
Source: The British Journal of Surgery - Category: Surgery Authors: Tags: Br J Surg Source Type: research
Abstract The incidence of brain metastases is increasing as cancer therapies improve and patients live longer, providing new challenges to the multidisciplinary teams that care for these patients. Brain metastatic cancer cells possess unique characteristics that allow them to penetrate the blood brain barrier, colonize the brain parenchyma, and persist in the intracranial environment. Additionally, brain metastases subvert the innate and adaptive immune system, permitting evasion of the anti-tumor immune response. Better understanding of the above mechanisms will allow for development and delivery of more effectiv...
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
In this study, analysis of antioxidant defense was performed on the blood samples from 184 "aged" individuals aged 65-90+ years, and compared to the blood samples of 37 individuals just about at the beginning of aging, aged 55-59 years. Statistically significant decreases of Zn,Cu-superoxide dismutase (SOD-1), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were observed in elderly people in comparison with the control group. Moreover, an inverse correlation between the activities of SOD-1, CAT, and GSH-Px and the age of the examined persons was found. No age-related changes in glutathione reductas...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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