Efficacy and safety of novel multifunctional M10 CAR-T cells in HIV-1-infected patients: a phase I, multicenter, single-arm, open-label study

Cell Discovery, Год журнала: 2024, Номер 10(1)

Опубликована: Май 14, 2024

Chimeric antigen receptor T (CAR-T) cells have been proposed for HIV-1 treatment but not yet demonstrated desirable therapeutic efficacy. Here, we report newly developed anti-HIV-1 CAR-T armed with endogenic broadly neutralizing antibodies (bNAbs) and the follicle-homing CXCR5, termed M10 cells. were designed to exercise three-fold biological functions, including broad cytotoxic effects on HIV-infected cells, neutralization of cell-free viruses produced after latency reversal, B-cell follicle homing. After demonstrating activities, administered treat 18 patients via a regimen two allogenic cell infusions an interval 30 days, each infusion followed by chidamide stimulations reservoir activation. Consequently, 74.3% resulted in significant suppression viral rebound, loads declining average 67.1%, 10 showed persistently reduced cell-associated RNA levels (average decrease 1.15 log10) over 150-day observation period. also found impose selective pressure latent reservoir. No treatment-related adverse observed. Overall, our study supported potential as novel, safe, effective option functional cure HIV-1/AIDS.

Язык: Английский

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A Review of FDA-Approved Anti-HIV-1 Drugs, Anti-Gag Compounds, and Potential Strategies for HIV-1 Eradication

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(7), С. 3659 - 3659

Опубликована: Март 25, 2024

Acquired immunodeficiency syndrome (AIDS) is an enormous global health threat stemming from human virus (HIV-1) infection. Up to now, the tremendous advances in combination antiretroviral therapy (cART) have shifted HIV-1 infection a fatal illness into manageable chronic disorder. However, presence of latent reservoirs, multifaceted nature HIV-1, drug resistance, severe off-target effects, poor adherence, and high cost restrict efficacy current cART targeting distinct stages life cycle. Therefore, there unmet need for discovery new therapeutics that not only bypass limitations but also protect body’s at same time. The main goal complete eradication purging latently infected cells patients’ bodies. A potential strategy called “lock-in apoptosis” targets budding phase cycle leads susceptibility apoptosis elimination reservoirs and, ultimately, eradication. work intends present advantages disadvantages United States Food Drug Administration (FDA)-approved anti-HIV-1 drugs as well plausible strategies design development more compounds with better potency, favorable pharmacokinetic profiles, improved safety issues.

Язык: Английский

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Changing epidemiology of COVID-19: potential future impact on vaccines and vaccination strategies

Expert Review of Vaccines, Год журнала: 2024, Номер 23(1), С. 510 - 522

Опубликована: Апрель 24, 2024

COVID-19 was an unprecedented challenge worldwide; however, disease epidemiology has evolved, and no longer constitutes a public health emergency of international concern. Nonetheless, remains global threat uncertainties remain, including definition the end pandemic transition to endemicity, understanding true rates SARS-CoV-2 infection/transmission.

Язык: Английский

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Evaluation of the Potency of Repurposed Antiretrovirals in HBV Therapy: A Narrative Investigation of the Traditional Medicine Alternatives

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(4), С. 1523 - 1523

Опубликована: Фев. 11, 2025

Hepatitis B is one of the killer communicable diseases, with a global estimation 1.1 million deaths resulting from liver diseases annually. The search for HBV therapeutics has resulted in repurposing existing antiretrovirals (ARVs) treatment, considering their shared common replication mechanisms. This review aimed at evaluating potencies some repurposed ARVs used analyzing mechanisms viral replications and HIV, investigating potentials traditional medicines as an alternative treatment patients. topical keywords drug repurposing, repositioning, antiretrovirals, hepatitis HBV, natural products, medicines, title, abstract were searched PubMed, Web Science, Google Scholar. advanced included five years, 2019-2024. result was filtered 377 to 110 relevant articles. evaluation reveals that CD4+ T cells are targeted by while targets its associated (cirrhosis hepatocellular carcinoma (HCC)). Furthermore, treatments available only prevent or slow down progression cirrhosis, reduce HCC incidence, can improve quality life increase expectancy; however, they not curative HBV. Traditional medicines/natural product extracts phytochemicals exert anti-HBV effects through different improved therapeutic when combined properly. investigation further consideration silico approach might streamline development but also contribute deeper understanding pathogenesis. Therefore, we recommend integration computational design methods medicine screening discovering new bioactive candidates.

Язык: Английский

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HIV Tissue Reservoirs: Current Advances in Research

AIDS Patient Care and STDs, Год журнала: 2023, Номер 37(6), С. 284 - 296

Опубликована: Май 15, 2023

Acquired immunodeficiency syndrome (AIDS), caused by the human virus (HIV), has become a heavy burden of disease and an important public health problem in world. Although current antiretroviral therapy (ART) is effective at suppressing blood, HIV still remains two different types reservoirs-the latently infected cells (represented CD4+ T cells) tissues containing those cells, which may block access to ART, HIV-neutralizing antibodies latency-reversing agents. The latter focus our review, as blood viral load drops below detectable levels after deeper more systematic understanding tissue reservoirs imperative. In this we take lymphoid system (including lymph nodes, gut-associated tissue, spleen bone marrow), nervous system, respiratory reproductive (divided into male female), urinary order, focusing on particularity importance each infection, infection target cell specific situation quantified DNA or RNA evidence compartmentalization pharmacokinetics. summary, found that present state both similarities differences. future, therapeutic principle need follow respect discrepancy basis grasping commonality. measures taken completely eliminate whole body cannot be generalized. It necessary formulate personalized treatment strategies according characteristics various tissues, so realize prospect curing AIDS soon possible.

Язык: Английский

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Harnessing antiviral RNAi therapeutics for pandemic viruses: SARS-CoV-2 and HIV

Drug Delivery and Translational Research, Год журнала: 2025, Номер unknown

Опубликована: Янв. 20, 2025

Abstract Using the knowledge from decades of research into RNA-based therapies, COVID-19 pandemic response saw rapid design, testing and production first ever mRNA vaccines approved for human use in clinic. This breakthrough has been a significant milestone RNA therapeutics vaccines, driving an exponential growth field. The development novel targeting high-threat pathogens, that pose substantial risk to global health, could transform future health delivery. In this review, we provide detailed overview two interference (RNAi) pathways how antiviral RNAi therapies can be used treat acute or chronic diseases caused by viruses SARS-CoV-2 HIV, respectively. We also insights short-interfering (siRNA) delivery systems, with focus on lipid nanoparticles functionalized achieve targeted specific sites disease. review will current developments HIV siRNAs, highlighting strategies advance progression siRNA along clinical pathway. Graphical

Язык: Английский

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Special Issue “The Role of Toll-Like Receptors (TLRs) in Infection and Inflammation 2.0”

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(17), С. 9709 - 9709

Опубликована: Сен. 7, 2024

Toll-like receptors (TLRs) are key players in the innate immune system, host’ first-line defense against pathogens [...]

Язык: Английский

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Recent advances in poor HIV immune reconstitution: what will the future look like?

Frontiers in Microbiology, Год журнала: 2023, Номер 14

Опубликована: Авг. 7, 2023

Combination antiretroviral therapy has demonstrated proved effectiveness in suppressing viral replication and significantly recovering CD4 + T cell count HIV type-1 (HIV-1)-infected patients, contributing to a dramatic reduction AIDS morbidity mortality. However, the factors affecting immune reconstitution are extremely complex. Demographic factors, co-infection, baseline level, abnormal activation, cytokine dysregulation may all affect reconstitution. According report, 10–40% of HIV-1-infected patients fail restore normalization function. They referred as immunological non-responders (INRs) who achieve complete have higher mortality rate risk developing other non-AIDS diseases compared with those Heretofore, mechanisms underlying incomplete remain elusive, INRs not effectively treated or mitigated. This review discusses recent progress responsible for summarizes corresponding therapeutic strategies according different improve individual therapy.

Язык: Английский

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Development of a LAMP-Based Diagnostic for the Detection of Multiple HIV-1 Strains

Biosensors, Год журнала: 2024, Номер 14(4), С. 157 - 157

Опубликована: Март 27, 2024

Since its first appearance in 1981, HIV-1 has remained a global concern. Current methods for diagnosing HIV-1, while effective, are mostly specific to given subtype of and often require expensive equipment highly trained individuals collect process the sample. It is necessary develop sensitive diagnostic method that can be administered with minimal provide better care low-resource settings. Loop-mediated isothermal amplification rapid detecting presence nucleic acid sequences. Herein we report development comparison two different HIV LAMP assays, integrase VPR, as well between TRIZol magnetic beads RNA extraction each assay. Our analysis shows assay was able detect virus from multiple subtypes under 30 min variable limit detection (LOD) dependent on subtype.

Язык: Английский

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CRISPR/Cas9 genome editing of CCR5 combined with C46 HIV-1 fusion inhibitor for cellular resistant to R5 and X4 tropic HIV-1

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Май 13, 2024

Abstract Hematopoietic stem-cell (HSC) transplantation using a donor with homozygous mutation in the HIV co-receptor CCR5 (CCR5Δ32/Δ32) holds great promise as cure for HIV-1. Previously, there were three patients that had been reported to be completely cured from infection by this approach. However, finding naturally suitable Human Leukocyte Antigen (HLA)-matched CCR5Δ32 is very difficult. The prevalence of allele only 1% Caucasian population. Therefore, additional sources CCR5Δ32/Δ32 HSCs are required. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated (Cas) system one method mediate knockout has successfully employed gene editing tool clinical trials. Additional anti-HIV-1 strategies still required broad-spectrum inhibition HIV-1 replication. Here study, we combined an therapy, which C46, cell membrane-anchored fusion inhibitor CRISPR/Cas9 mediated CCR5. therapeutic genes investigated potential prevention both (R5)- and CXCR4 (X4)-tropic infections MT4CCR5 line. combinatorial therapies superior compared single therapy achieving strategy shows future applications.

Язык: Английский

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