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Switch receptor T3/28 improves long-term persistence and anti-tumor efficacy of CAR-T cells

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Switch receptor T3/28 improves long-term persistence and ant...

Vaccinia virus viability under different environmental conditions and different disinfectants treatment

第十四届全国免疫学学术大会

作者： Songbo Zhao Xiaohong Liang Chunhong Ma Lifen Gao Key Laboratory for Experimental Teratology of Ministry of Education Shandong Key Laboratory of Infection and Immunityand Department of ImmunologySchool of Basic Medical SciencesCheeloo College of MedicineShandong University

Background:Chimeric antigen receptor(CAR) T cells have been successfully used in tumor immunotherapy by driving strong antitumor responses,especially in the setting of hematological malignancies such as B cell acute lymphoid leukemia(B-ALL).H owever,on target/off tumor and poor persistence severely limit application of CAR-T cell therapy in clinical and little is known about the impact of switch receptor on persistence of CAR-T ***:T cell immunoglobulin mucin domain molecule 3(TIM-3) was included to develop a second generation 41 BB CD19 CAR linked with a T3/28 chimera,in which truncated extracellular TIM-3 was fused with the CD28 transmembrane and cytoplasmic *** efficacy of T3/28 CAR-T cells was evaluated in vitro and in ***:We demonstrated that switch receptor T3/28 preserved the TCM phenotype,improved proliferative capacity and reduced exhaustion of CAR-T cells,which resulted in superior in vitro antitumor activity in B *** addition,switch receptor T3/28 enhances the cytotoxicity ability of 19 BBz CAR-T cells depending on TIM-3 *** the same time,switch receptor T3/28 mediates superior anti-tumor cytotoxicity against blood tumor and solid tumor,showing that T3/28 CAR-T cell treatment significantly led to reduction in tumor burden and improvement in ***,switch receptor T3/28 substantially prolonged persistence of CAR-T cells in B lymphoma and multiple myeloma bearing mice,and IL-21/Stat3 axis probably contributed to the enhanced cytotoxicity of T3/28 CAR-T ***:Overall,T3/28 CAR-T cells maintain a superior phenotype and switch receptor T3/28 significantly prolongs the persistence of CAR-T cells,and T3/28 CAR-T cells possess much potent antitumor activity in mice,which would shed new lights on the improvements of adoptive T cell therapies.

关键词： CAR-T switch receptor TIM-3 persistence

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Biosafety and Health 2024年第1期6卷 21-27页

作者： Shan Mei Liang Wei Yu Xie Fei Zhao Yu Huang Zhangling Fan Yamei Hu Liming Wang Lingwa Wang Ying Wang Fengwen Xu Fei Guo NHC Key Laboratory of Systems Biology of Pathogens National Institute of Pathogen Biology and Center for AIDS ResearchChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Department of Otolaryngology Head and Neck Surgery Beijing Tongren HospitalCapital Medical UniversityBejing 100730China Clinical Laboratory Emergency General HospitalBeijing 100028China

Monkeypox(mpox)outbreak in 2022 has caused more than 91,000 cases,has spread to 115 countries,regions,and territories,and has thus attracted much *** stability of poxvirus particles in the environment is recognized as an important factor in determining their ***,few studies have investigated the persistence of poxviruses on material surfaces under various environmental conditions,and their sensitivity to ***,we systematically measured the stability of vaccinia virus(VACV)under different environmental conditions and sensitivity to inactivation methods via plaque assay,quantitative real‐time polymerase chain reaction(qPCR),and Gaussia luciferase(G‐luciferase)reporter *** results show that VACV is stable on the surface of stainless steel,glass,clothing,plastic,towel,A4 paper,and tissue and persists much longer at 4℃ and?20℃,but is effectively inactivated by ultraviolet(UV)irradiation,heat treatment,and chemical *** study raises the awareness of long persistence of poxviruses in the environment and provides a simple solution to inactivate poxviruses using common disinfectants,which is expected to help the control and prevention of mpox virus and future poxvirus outbreaks.

关键词： Poxvirus Mpox virus Vaccinia virus persistence Disinfectant

How virus persistence can initiate the tumorigenesis process

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World Journal of Virology 2013年第2期2卷 102-109页

作者： Simone Avanzi Gualtiero Alvisi Alessandro Ripalti Department of Oncology Hematology and Laboratory Medicine Operative Unit of Microbiology A.O-U. di Bologna Policlinico S. Orsola-Malpighi 40138 Bologna Italy Department of Molecular Medicine Microbiology Section University of Padua

Human oncogenic viruses are defined as necessary but not sufficient to initiate cancer. Experimental evidence suggests that the oncogenic potential of a virus is effective in cells that have already accumulated a number of genetic mutations leading to cell cycle deregulation. Current models for viral driven oncogenesis cannot explain why tumor development in carriers of tumorigenic viruses is a very rare event, occurring decades after virus infection. Considering that viruses are mutagenic agents per se and human oncogenic viruses additionally establish latent and persistent infections, we attempt here to provide a general mechanism of tumor initiation both for RNA and DNA viruses, suggesting viruses could be both necessary and sufficient in triggering human tumorigenesis initiation. Upon reviewing emerging evidence on the ability of viruses to induce DNA damage while subverting the DNA damage response and inducing epigenetic disturbance in the infected cell, we hypothesize a general, albeit inefficient hit and rest mechanism by which viruses may produce a limited reservoir of cells harboring permanent damage that would be initiated when the vi-rus first hits the cell, before latency is established. Cells surviving virus generated damage would consequently become more sensitive to further damage mediated by the otherwise insufficient transforming activity of virus products expressed in latency, or upon episodic reactivations(viral persistence). Cells with a combination of genetic and epigenetic damage leading to a cancerous phenotype would emerge very rarely, as the probability of such an occurrence would be dependent on severity and frequency of consecutive hit and rest cycles due to viral reinfections and reactivations.

关键词： Virus Carcinogenesis Tumor Oncogene Latency Viral persistence

CONTROL STRATEGIES FOR A TUMOR-IMMUNE SYSTEM WITH IMPULSIVE DRUG DELIVERY UNDER A RANDOM ENVIRONMENT

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Acta Mathematica Scientia 2022年第3期42卷 1141-1159页

作者： Mingzhan HUANG Shouzong LIU Xinyu SONG Xiufen ZOU College of Mathematics and Statistics Xinyang Normal UniversityXinyang 464000China School of Mathematics and Statistics Computational Science Hubei Key LaboratoryWuhan UniversityWuhan 430072China

This paper mainly studies the stochastic character of tumor growth in the presence of immune response and periodically pulsed ***,a stochastic impulsive model describing the interaction and competition among normal cells,tumor cells and immune cells under periodically pulsed chemotherapy is ***,sufficient conditions for the extinction,non-persistence in the mean,weak and strong persistence in the mean of tumor cells are ***,numerical simulations are performed which not only verify the theoretical results derived but also reveal some specific *** results show that the growth trend of tumor cells is significantly affected by the intensity of noise and the frequency and dose of drug *** clinical practice,doctors can reduce the randomness of the environment and increase the intensity of drug input to inhibit the proliferation and growth of tumor cells.

关键词： Tumor-immune system chemotherapy stochastic impulsive model extinction persistence

Understanding neutralising antibodies against SARS-CoV-2 and theirimplications in clinical practice

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Military Medical Research 2022年第2期9卷 215-230页

作者： Natalie Yan-Lin Pang Alexander Shao-Rong Pang Vincent T.Chow De-Yun Wang Yong Loo Lin School of Medicine National University of SingaporeSingapore 119228Singapore Department of Microbiology and Immunology National University of SingaporeScience Drive 2Singapore 117545Singapore Infectious Diseases Translational Research Program Yong Loo Lin School of MedicineNational University of SingaporeSingapore 119228Singapore Department of Otolaryngology Yong Loo Lin School of MedicineNational University of Singapore1E Kent Ridge RoadSingapore 119228Singapore

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is a newly identified member of the coronavirus family that has caused the coronavirus disease 2019 (COVID-19) pandemic. This rapidly evolving and unrelenting SARS-CoV-2has disrupted the lives and livelihoods of millions worldwide. As of 23 August 2021, a total of 211,373,303 COVID-19cases have been confirmed globally with a death toll of 4,424,341. A strong understanding of the infection pathway of SARS-CoV-2, and how our immune system responds to the virus is highly pertinent for guiding the development and improvement of effective treatments. In this review, we discuss the current understanding of neutralising antibodies(NAbs) and their implications in clinical practice. The aspects include the pathophysiology of the immune response,particularly humoral adaptive immunity and the roles of NAbs from B cells in infection clearance. We summarise the onset and persistence of IgA, IgM and IgG antibodies, and we explore their roles in neutralising SARS-CoV-2, their persistence in convalescent individuals, and in reinfection. Furthermore, we also review the applications of neutralising antibodies in the clinical setting—from predictors of disease severity to serological testing to vaccinations, and finally in therapeutics such as convalescent plasma infusion.

关键词： Severe acute respiratory syndrome coronavirus Coronavirus disease 2019 Neutralising antibodies persistence Spike glycoprotein Receptor-binding domain B cells T cells Convalescent plasma

Sorption and desorption behavior of residual antidepressants and caffeine in freshwater sediment and sewage sludge

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International Journal of Sediment Research 2022年第3期37卷 346-354页

作者： Ismael Laurindo Costa Junior Christiane Schinneider Machado Adelmo Lowe Pletsch Yohandra Reyes Torres Department of Chemistry Federal University of Technology-Paraná (UTFPR) Department of Chemistry State University of Midwest (UNICENTRO)

The use of antidepressants is widespread in modern times. Thus, they present a potential risk for ecosystems due to occurrence in domestic sewage containing unaltered metabolites and structures, even after the treatment plants have processed the sewage. The current research investigated the sorption and desorption of antidepressants(citalopram, venlafaxine, fluoxetine, sertraline, and amitriptyline) and caffeine from freshwater sediment and sewage sludge. The samples of freshwater sediment were collected in a river spring in an area with few anthropogenic sources of pollution and samples of sewage sludge were taken from stabilization ponds of a sewage treatment. The matrices were mainly composed of organic fractions, sediment of humic nature, and aliphatic biomolecules in sludges. The presence of silt and clay in the sediment proved to be important for the sorption process when compared to the flocs and colloidal structure of the sludge. The kinetic study indicated pseudo-first order behavior. The Freundlich isotherm was satisfactorily used in the interpretation of sorption and desorption for all analytes and matrices. The high percentages obtained for desorption suggest analyte mobility, which is more intense in the sludge than in the sediment since each matrix has a different composition. It can be considered that the information obtained here reinforces the ecotoxicological concern with respect to pharmacological residues in the environment, as processes of retention by sorption in the sludge and the sediment have been confirmed, as well as the preferential partition of some analytes by the aqueous phase.

关键词： Emerging pollutants Drugs persistence Partition Mobility Sorption

The effect of interference time in a predator–prey–nonprey system

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International Journal of Modeling, Simulation, and Scientific Computing 2022年第3期13卷 230-244页

作者： Debasis Mukherjee Department of Mathematics Vivekananda College ThakurpukurKolkata 700063India

In this paper,we propose a three-species model consisting of two competing(prey and nonprey)species and a predator ***,nonprey species are not included in the predator’s food *** competition process follows Holling type II competitive response to interference *** results include the stability of the ***,it is established that an increasing number of interference time stabilizes the ***,it is shown that the interference time has an impact on the predator equilibrium ***,we develop the criterion of persistence of all the *** is also shown that the system may not be persistent when multiple steady states *** examine the global stability of the coexistence equilibrium *** experiments are carried out to understand the analytical outcomes.

关键词： Interference time predator-prey-nonprey interaction stability bifurcation persistence

A regime-switching stochastic SIR epidemic model with a saturated incidence and limited medical resources

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生物数学学报:英文版 2023年第7期16卷 91-110页

作者： Wei Wei Wei Xu Jiankang Liu Department of Applied Mathematics Northwestern Polytechnical University Xi'an 710072 ShaanciP.R.China

The stochastic switching SIR epidemic model with saturated incidence and limited medical treatment is investigated in this *** using Lyapunov methods and Ito formula,we first prove that the system has a unique global positive solution with any positive initial *** combining inequality technique and the ergodic property of Markov switching,the suficient conditions for extinction and persistence in the mean of the disease are *** results demonstrate that increasing medical resources and improving supply efficiency can accelerate the transition from the persistent state to the extinct ***,the high incidence rate will slow down the extinction of the ***,the switching noise can induce the system to toggle between the extinct and persistent ***,some numerical simulations are carried out to confirm the analytical results.

关键词： Epidemic model extinction persistence Markov switching saturated incidence

HP0953-hypothetical virulence factor overexpresion and localization during Helicobacter pylori infection of gastric epithelium

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World Journal of Gastroenterology 2022年第29期28卷 3886-3902页

作者： Nancy K Arteaga-Resendiz Gerardo E Rodea Rosa María Ribas-Aparicio Alma L Olivares-Cervantes Juan Arturo Castelán-Vega Joséde Jesús Olivares-Trejo Sandra Mendoza-Elizalde Edgar O López-Villegas Christian Colín Pamela Aguilar-Rodea Alfonso Reyes-López Marcela Salazar García Norma Velázquez-Guadarrama Laboratorio de Investigación en Enfermedades Infecciosas Hospital Infantil de México Federico GómezMexico City 06720Mexico Posgrado en Biomedicina y Biotecnología Molecular Laboratorio de Producción y Control de BiológicosEscuela Nacional de Ciencias BiológicasInstituto Politécnico NacionalMexico City 11340Mexico Laboratorio de Adquisición de Hierro Universidad Autónoma de la Ciudad MéxicoPosgrado Ciencias GenómicaMexico City 03100Mexico Laboratorio Central de Microscopía Escuela Nacional de Ciencias BiológicasInstituto Politécnico NacionalMexico City 11340Mexico Centro de estudios económicos y sociales en salud Hospital Infantil de México Federico GómezMexico City 06720Mexico Laboratorio de Investigación en Biología del Desarrollo y Teratogénesis Experimental Hospital Infantil de México Federico GómezMexico City 06720Mexico

BACKGROUND The high prevalence and persistence of Helicobacter pylori(H. pylori) infection, as well as the diversity of pathologies related to it, suggest that the virulence factors used by this microorganism are varied. Moreover, as its proteome contains 340hypothetical proteins, it is important to investigate them to completely understand the mechanisms of its virulence and survival. We have previously reported that the hypothetical protein HP0953 is overexpressed during the first hours of adhesion to inert surfaces, under stress conditions, suggesting its role in the environmental survival of this bacterium and perhaps as a virulence *** To investigate the expression and localization of HP0953 during adhesion to an inert surface and against gastric(AGS) *** Expression analysis was performed for HP0953 during H. pylori adhesion. HP0953 expression at 0,3, 12, 24, and 48 h was evaluated and compared using the Kruskal-Wallis equality-of-populations rank test. Recombinant protein was produced and used to obtain polyclonal antibodies for immunolocalization. Immunogold technique was performed on bacterial sections during adherence to inert surfaces and AGS cells, which was analyzed by transmission electron microscopy. HP0953 protein sequence was analyzed to predict the presence of a signal peptide and transmembrane helices, both provided by the ExPASy platform, and using the GLYCOPP platform for glycosylation sites. Different programs, via, I-TASSER, RaptorX, and HHalign-Kbest, were used to perform three-dimensional *** HP0953 exhibited its maximum expression at 12 h of infection in gastric epithelium *** technique revealed HP0953 localization in the cytoplasm and accumulation in some peripheral areas of the bacterial body, with greater expression when it is close to AGS *** analysis revealed the presence of a signal peptide that interacts with the transmembrane region and then allows the release of the protein

关键词： Hypothetical protein HP0953 Adherence Helicobacter pylori Glycocalyx Virulence factor persistence