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Colorectal carcinoma (CRC) is one of the most common malignant cancers worldwide. The poor response of CRC to chemotherapy has whipped up the interest in targeted therapy with monoclonal antibodies for its potential efficiency. However, cetuximab, as one of the first-line targeted drugs in the treatment of CRC, has drug resistance and poor prognosis in clinic. To address this, a novel bispecific protein with CRC targeting and natural killer (NK) cell triggering was used for treatment. NK cell-mediated immunosurveillance is normally activated by the activating receptor natural killer cell receptor NK group 2, member D (NKG2D), which binds its key ligand major histocompatibility complex (MHC) class I-related chain A (MICA) expressed on the tumor cells. To trigger NK cell-mediated cytotoxicity, we fused MICA portion to a single-chain antibody fragment rG7S targeting the tumor-associated antigen CD24. In vitro, flow cytometry, cytotoxicity assay, degranulation, and cytokines release assay revealed that the fusion protein rG7S-MICA could both binds to CD24 and NKG2D which enhances NK cell sensitivity and NKG2D-mediated immunosurveillance against CD24 CRC cells. Furthermore, in a CD24 CRC-bearing nude mice model, rG7S-MICA effectively recruits NK cell to the tumor site and increase the release of cytokines such as interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), and shows potential antitumor effects. In conclusion, rG7S-MICA provides a novel immunotherapeutic strategy for CRC, which could be further developed against other CD24 malignancies.
This article was published in the following journal.
Name: Journal of immunotherapy (Hagerstown, Md. : 1997)
Natural killer (NK) cells are important innate cytotoxic lymphocytes that have potential in treatment of leukemia. Engagement of NKG2D receptor on NK cells enhances the target cytotoxicity. Here we pr...
The natural killer group 2D (NKG2D) receptor on natural killer (NK) cells play an important role in immunosurveillance to cancer cells, which could mediate the eradication of tumor cells through speci...
Inhibition of protease-driven MICA and MICB shedding enhances NK cell-mediated tumor immunity.
In this review, we specifically focus on genetic modifications of oncolytic adenovirus 5 (Ad5)-based vectors that enhance replication, oncolysis/spread, and virus-mediated tumor immunosurveillance. Th...
In this work, the removal of different types of emerging pollutants (four perfluoroalkyl compounds, two preservatives, three surfactants and nine pharmaceutical compounds) from aqueous solution by ads...
A Prospective Study on the Efficacy and Safety of CD8+NKG2D+ AKT cell immunotherapy to the pancreatic cancer patients treated with adjuvant chemotherapy.
This is a single-centre, single arm, open-label pilot study to evaluate the safety and feasibility of CAR-NK cell treatment in subjects with metastatic solid tumours. Autologous or allogen...
The probability of pCR in Triple Negative Breast Cancer patients receiving standard of care AC-T neoadjuvant chemotherapy is associated with the dominance of specific intestinal microbiota...
The purpose of this study is to examine the transition of offenders with both mental illness and chemical abuse (MICA) disorders from prison to the community, where continued treatment is ...
In vitro statins, inhibitors of the HMG-CoA-reductase, have been shown to overcome cell adhesion mediated drug resistance at very low concentrations. The purpose of the study is to investi...
An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activa
Glycoproteins with a wide distribution on hematopoietic and non-hematopoietic cells and strongly expressed on macrophages. CD58 mediates cell adhesion by binding to CD2; (ANTIGENS, CD2); and this enhances antigen-specific T-cell activation.
Glycoproteins with a wide distribution on hematopoietic and non-hematopoietic cells and strongly expressed on MACROPHAGES. CD58 mediates cell adhesion by binding to CD2; (CD2 ANTIGENS); and this enhances antigen-specific T-cell activation.
The phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface IMMUNOGLOBULIN G whose Fc portion is intact. The effector cell is a "killer" cell possessing Fc receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent.
Biological therapy involves the use of living organisms, substances derived from living organisms, or laboratory-produced versions of such substances to treat disease. Some biological therapies for cancer use vaccines or bacteria to stimulate the body&rs...