T and NK cells armed with chimeric antigen receptors (CAR) are promising tools for the specific elimination of cancer cells. In most CAR designs implemented to date, the recognition of target cells ...is mediated by single-chain variable fragments (scFvs) derived from murine monoclonal antibodies. This format, however, has a number of limitations, including its relatively large size and potential immunogenicity in humans. In this study, we explored the feasibility of using human fibronectin type III domains (Fn3) as the antigen recognition domain in CARs. Human Fn3 domains have lower predicted immunogenicity compared to mouse-derived sequences, and a reduced molecular weight compared to scFvs. We created a functional CAR using a VEGFR2-specific Fn3 module replacing the conventional scFv. The resulting FnCAR specifically potentiates the cytotoxic activity of human T cells and YT NK cells in the presence of VEGFR2-positive targets. These findings demonstrate that Fn3 domains can be used in CARs for antigen recognition.
The properties of the boundary lubricating films determine the performance of friction units, which is most important in the event of a loss of lubricant. It has been found that when sunflower oil is ...added to mineral transmission oil, strong boundary layers are formed during friction. These layers reduce wear and friction. Vegetable oils with the lowest iodine value have the best antiwear properties. The additional introduction of the product of the interaction of rosin with copper (II) hydroxide into the transmission oil makes it possible to form lubricating structured layers that improve the tribotechnical properties.
Early results from clinical trials of autologous chimeric antigen receptor (CAR)-expressing T cells for the therapy of B-cell malignancies have encouraged extending the potency of this therapy to ...other cancers. However, the success of using CAR T-cells to treat patients with solid tumors has been limited. In this review, we summarize current knowledge on the design and applications of CARs for the targeted therapy of cancer. We describe existing issues that limit the widespread application of CAR T cells and discuss the optimization steps needed to further improve safety and efficacy of this therapeutic platform.
Chimeric antigen receptors (CARs) are recombinant protein molecules that redirect cytotoxic lymphocytes toward malignant and other target cells. The high feasibility of manufacturing CAR-modified ...lymphocytes for the therapy of cancer has spurred the development and optimization of new CAR T cells directed against a broad range of target antigens. In this review, we describe the main structural and functional elements constituting a CAR, discuss the roles of these elements in modulating the anti-tumor activity of CAR T cells, and highlight alternative approaches to CAR engineering.
COVID-19 is a new epidemic infectious disease characterized by a relatively high contagiousness and the likelihood of life-threatening complications in the form of acute respiratory distress syndrome ...(ARDS), acute respiratory and multiple organ failure. The causative agent of the disease is the enveloped zoonotic RNA virus SARS-CoV-2 belongs to the Coronaviridae family, the genus Betacoronavirus, as well as the previously known SARS-CoV and MERS-CoV viruses, which cause severe acute respiratory syndrome and the Middle East respiratory syndrome, respectively. The virus is transmitted by air and contact routes, therefore, to protect medical personnel it is necessary to use individual protective suits and accessories, with protection of the respiratory tract and eyes, disinfection of hands and surfaces as when working with microorganisms of the I-II pathogenicity group. The diagnosis of COVID-19 is confirmed using real-time RT-PCR diagnostics that detect the presence of viral RNA. The clinical manifestations of COVID-19 vary from mild to moderate, to severe and extremely severe (5% of cases, ARDS, multiple organ failure, mechanical ventilation and resuscitation are necessary). The clinical picture of acute respiratory viral infections with severe fever, dry cough, respiratory failure, against the background of lymph and thrombocytopenia, normal procalcitonin, elevated levels of ferritin and CRP in the blood with signs of bilateral, polysegmental pneumonia and the phenomenon of "frosted glass" on CT, even in the absence of an unfavorable epidemiological An anamnesis makes it possible to diagnose COVID-19 with a high degree of probability and hospitalize the patient in an infectious isolation ward, without waiting for the results of PCR diagnostics. There is no specific etioptropic therapy for COVID-19; the only method that has proven effective in limited clinical trials is plasma infusion of convalescents with a high titer of neutralizing antibodies. High hopes are pinned on innovative treatments, such as the creation of neutralizing monoclonal antibodies and cell therapy using MSCs or NK cells. The first SARS-CoV-2 vaccine, mRNA-1273, is currently undergoing clinical trials.
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