Next-generation treatments: Immunotherapy and advanced therapies for COVID-19

Heliyon, Journal Year: 2024, Volume and Issue: 10(5), P. e26423 - e26423

Published: Feb. 19, 2024

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in 2019 following prior outbreaks of coronaviruses like SARS and MERS recent decades, underscoring their high potential infectivity humans. Insights from previous have played a significant role developing effective strategies to mitigate the global impact SARS-CoV-2. As January 7, 2024, there been 774,075,242 confirmed cases worldwide. To date, 13.59 billion vaccine doses administered, 7,012,986 documented fatalities (https://www.who.int/)Despite progress addressing rapid evolution SARS-CoV-2 challenges human defenses, presenting ongoing challenges. emergence new lineages, shaped mutation recombination processes, has led successive waves infections. This scenario reveals need for next-generation vaccines as crucial requirement ensuring protection against demand calls formulations that trigger robust adaptive immune response without leading inflammation linked with infection.Key mutations detected Spike protein, critical target neutralizing antibodies design —specifically within Receptor Binding Domain region Omicron variant lineages (B.1.1.529), currently dominant worldwide, intensified concerns due association immunity evasion vaccinations infections.As world deals this evolving threat, narrative extends realm emerging variants, each displaying implications remain largely misunderstood. Notably, JN.1 lineage is gaining prevalence, early findings suggest it stands among immune-evading characteristic attributed its L455S. Moreover, detrimental consequences novel bear particularly on immunocompromised individuals older adults. Immunocompromised face such suboptimal responses vaccines, rendering them more susceptible disease. Similarly, adults an increased risk disease presence comorbid conditions, find themselves at heightened vulnerability develop Thus, recognizing these intricate factors effectively tailoring public health protect vulnerable populations. In context, review aims describe, analyze, discuss current treatments encompassing immunotherapeutic approaches advanced therapies complements will offer solutions counter disadvantages existing options. Preliminary outcomes show virus address immunomodulatory associated COVID-19. Furthermore, capacity promote tissue repair demonstrated, which can be noteworthy who stand actors landscape possess broader potential, offering wide range variants enhancing ability constant virus. are projected treatment alternatives managing Chronic Post-COVID-19 syndromeand long-term complications.

Language: Английский

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Recent advances of CAR-T cells in acute myeloid leukemia

Therapeutic Advances in Hematology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 1, 2025

Acute myeloid leukemia (AML), the most common type of in adults, is a highly heterogeneous and aggressive hematologic malignancy. Since 20th century, combination cytosine arabinoside anthracyclines has been chemotherapy drug used to treat patients with AML. Although, new targeted medicines have emerged, such as midostaurin gilteritinib targeting FMS-like tyrosine kinase 3 (FLT3), ivosidenib (isocitrate dehydrogenase 1 (IDH1) inhibitor) enasidenib (IDH2 IDH, gemtuzumab ozogamicin CD33, which changed treatment strategies But, until now, hematopoietic stem cell transplantation remains best option cases. However, resistance relapse are still major consequences disease progression AML, highlighting urgent need for novel therapeutic approaches. As an alternative, chimeric antigen receptor (CAR)-T cells engineered T-cells developed breakthrough cancer therapy recent years, explored various tumor types. In particular, it achieved remarkable efficacy field relapsed refractory B lymphocyte tumors. This review mainly summarizes discusses research progress clinical application CAR-T immunotherapy AML years.

Language: Английский

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Chimeric Antigen Receptor T Cell and Chimeric Antigen Receptor NK Cell Therapy in Pediatric and Adult High-Grade Glioma—Recent Advances

Cancers, Journal Year: 2024, Volume and Issue: 16(3), P. 623 - 623

Published: Jan. 31, 2024

High-grade gliomas (HGG) account for approximately 10% of central nervous system (CNS) tumors in children and 25% CNS adults. Despite their rare occurrence, HGG are a significant clinical problem. The standard therapeutic procedure both pediatric adult patients with is the surgical resection tumor combined chemotherapy radiotherapy. intensive treatment, 5-year overall survival below 20–30%. This rate even lower most common adults (glioblastoma), at less than 5%. It is, therefore, essential to search new methods that can extend rate. One options use immune cells (T lymphocytes/natural killer (NK) cells) expressing chimeric antigen receptor (CAR). objective following review present latest results preclinical studies evaluating efficacy CAR-T CAR-NK therapy.

Language: Английский

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Chimeric antigen receptor (CAR) modified T Cells in acute myeloid leukemia: limitations and expectations

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: April 17, 2024

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with a poor prognosis despite the advent of novel therapies. Consequently, major need exists for new therapeutic options, particularly patients relapsed/refractory (R/R) AML. In recent years, it has been possible to individualize treatment subgroup patients, emergence multiple targeted Nonetheless, considerable number remain without and overall remains because high rate disease relapse. this sense, cellular therapies, especially chimeric antigen receptor (CAR)-T cell therapy, have dramatically shifted options other malignancies, such as diffuse large B lymphoma acute lymphoblastic leukemia. contrast, effectively treating AML CAR-based immunotherapy poses biological clinical challenges, most them derived from unmet identify target antigens expression restricted blast compromising viability normal hematopoietic stem counterpart. Although those limitations hampered CAR-T therapy translation clinic, there are several trials where antigens, CD123, CLL-1 or CD33 being used treat showing promising results. Moreover, continuing efforts enhance specificity efficacy in These endeavors encompass exploration avenues, including development dual cells next-generation cells, well utilization gene editing tools mitigate off-tumor toxicities. review, we will summarize ongoing studies early results reported AML, highlight approaches overcome these barriers. We also discuss how when should be context

Language: Английский

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Advances in Drug Delivery Systems for the Treatment of Acute Myeloid Leukemia

Small, Journal Year: 2024, Volume and Issue: 20(42)

Published: June 27, 2024

Acute myeloid leukemia (AML) is a common and catastrophic hematological neoplasm with high mortality rates. Conventional therapies, including chemotherapy, hematopoietic stem cell transplantation (HSCT), immune therapy, targeted agents, have unsatisfactory outcomes for AML patients due to drug toxicity, off-target effects, resistance, side relapse refractoriness. These intrinsic limitations of current treatments promoted the development application nanomedicine more effective safer therapy. In this review, classification nanoparticles applied in liposomes, polymersomes, micelles, dendrimers, inorganic nanoparticles, reviewed. addition, various strategies enhancing therapeutic targetability nanomedicine, use conjugating ligands, biomimetic-nanotechnology, bone marrow targeting, which indicates potential reverse are discussed. The assisting immunotherapy also involved. Finally, advantages possible challenges transition from preclinical phase clinical

Language: Английский

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Clinical Implications of Isocitrate Dehydrogenase Mutations and Targeted Treatment of Acute Myeloid Leukemia with Mutant Isocitrate Dehydrogenase Inhibitors—Recent Advances, Challenges and Future Prospects

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7916 - 7916

Published: July 19, 2024

Despite the better understanding of molecular mechanisms contributing to pathogenesis acute myeloid leukemia (AML) and improved patient survival in recent years, AML therapy still remains a clinical challenge. For this reason, it is important search for new therapies that will enable achievement remission. Recently, Food Drug Administration approved three mutant IDH (mIDH) inhibitors treatment AML. However, use mIDH monotherapy usually leads development resistance subsequent recurrence cancer, despite initial effectiveness therapy. A complete by which mutations influence leukemia, as well processes inhibitors, may significantly improve efficacy through an appropriate synergistic approach. The aim literature review present role IDH1/IDH2 results trials using mIDH1/IDH2 discuss challenges related practice future prospects potential methods overcoming these agents.

Language: Английский

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The Implementation of Chimeric Antigen Receptor (CAR) T-cell Therapy in Pediatric Patients: Where Did We Come From, Where Are We Now, and Where are We Going?

Clinical Hematology International, Journal Year: 2024, Volume and Issue: 6(1)

Published: March 13, 2024

CD19-directed Chimeric Antigen Receptor (CAR) T-cell therapy has revolutionized the treatment of patients with B-cell acute lymphoblastic leukemia (B-ALL). Somewhat uniquely among oncologic clinical trials, early development occurred simultaneously in both children and adults. In subsequent years however, larger number adult relapsed/refractory (r/r) malignancies led to accelerated multiple CAR products that target a variety malignancies, resulting six currently FDA-approved for patients. By comparison, only single CAR-T cell is approved by FDA pediatric patients: tisagenlecleucel, which ≤ 25 refractory precursor ALL, or ALL second later relapse. Tisagenlecleucel also under evaluation non-Hodgkin lymphoma, but not yet been this indication. All other therapies available (axicabtagene ciloleucel, brexucabtagene autoleucel, lisocabtagene maraleucel) are investigations children, preliminary results some cases. As volume complexity data continue grow, so too does necessity rapid assimilation implementation those data. This particularly true when considering “atypical” situations, e.g. arising do precisely conform profile included pivotal alternative options (e.g. hematopoietic stem transplantation (HSCT) bispecific engagers (BITEs)) available. We have therefore developed relevant summary literature pertaining use patients, sought provide guidance clinicians seeking additional about specific situations.

Language: Английский

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Therapeutic Targeting of TIM-4-L with Engineered T Cells for Acute Myeloid Leukemia

Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 30(9), P. 1878 - 1888

Published: March 7, 2024

Abstract Purpose: Disruption of lipid bilayer asymmetry is a common feature observed in cancer cells and offers novel routes for therapeutic targeting. We used the natural immune receptor TIM-4 to interrogate loss plasma membrane phospholipid polarity primary acute myelogenous leukemia (AML) samples evaluated anti-leukemic activity TIM-4-L–directed T-cell therapy preclinical AML models. Experimental Design: performed FACS analysis on 33 bone marrow specimens correlated TIM-4-L expression frequency intensity with molecular disease characteristics. Using Kasumi-1 MV-4–11 cell lines, we further tested effects engineered T vitro vivo. Results: found that 86% untreated blasts displayed upregulation surface TIM-4-L. These observations were agnostic genetic classification, as mutations TP53, ASXL1, RUNX1 similar seen favorable intermediate subtypes. dysregulation was also stably present lines. To evaluate potential targeting upregulated adoptive therapy, constructed cells, which demonstrated potent effects, effectively eliminating lines range endogenous levels both Conclusions: results highlight highly prevalent target across classifications T-cell–based AML. Further investigations into role pathogenesis its an clinical development are warranted.

Language: Английский

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Unveiling the Role of New Molecules in Acute Myeloid Leukemia: Insights into Disease Pathogenesis and Therapeutic Potential

Targets, Journal Year: 2024, Volume and Issue: 2(4), P. 396 - 427

Published: Nov. 20, 2024

This review article explores the current landscape of acute myeloid leukemia treatment, including novel target molecules and recent advancements in cell therapy immunotherapy focused on T activity. Advances treatment have been promising years, driven by development therapies targeting new molecular genetic therapeutic targets. These findings allowed for approval several European American drug agencies last 5 years. However, mortality remains very high, particularly relapsed or refractory (R/R) patients. In has expanded this field, leading to introduction drugs treatments.

Language: Английский

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Therapeutic Targeting of TIM-4-L With Engineered T Cells for Acute Myeloid Leukemia

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 4, 2023

Abstract Disruption of the lipid asymmetric bilayer is a common feature observed in cancer cells. We utilized natural immune receptor TIM-4 to interrogate for loss plasma membrane phospholipid polarity primary acute myelogenous leukemia (AML) samples. performed FACs analysis 33 patients and correlated TIM-4-L expression frequency intensity with molecular disease characteristics. In normal tissues, confined internal leaflet membrane. By contrast, 86% untreated AML blasts our displayed upregulation cell surface TIM-4-L. These observations were agnostic genetic classification, as samples mutations TP53, ASXL1 , RUNX1 also similar that seen favorable intermediate subtypes. This dysregulation was stably present both Kasumi-1 MV-4-11 lines. To evaluate potential upregulated serve target adoptive T therapy (ACT), we constructed TIM-4-L-directed engineered cells, which demonstrated potent anti-leukemic effects, effectively eliminating lines vitro vivo. approach led eradication cells across range endogenous levels. results highlight highly prevalent novel cell-based AML. Further investigations into role pathogenesis its an clinical development are warranted.

Language: Английский

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