Complete spectrum of adverse events associated with chimeric antigen receptor (CAR)-T cell therapies DOI Creative Commons
Chieh Yang, John Nguyen, Yun Yen

et al.

Journal of Biomedical Science, Journal Year: 2023, Volume and Issue: 30(1)

Published: Oct. 21, 2023

Abstract Chimeric antigen receptor (CAR)-T cell therapies have been approved by FDA to treat relapsed or refractory hematological malignancies. However, the adverse effects of CAR-T are complex and can be challenging diagnose treat. In this review, we summarize major events, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity (ICANS), CAR T-cell associated HLH (carHLH), discuss their pathophysiology, symptoms, grading, diagnosis systems, as well management. a future outlook, also provide an overview measures modifications cells that currently being explored limit toxicity.

Language: Английский

Harnessing the potential of CAR-T cell therapy: progress, challenges, and future directions in hematological and solid tumor treatments DOI Creative Commons

Gunjan Dagar,

Ashna Gupta,

Tariq Masoodi

et al.

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: July 7, 2023

Abstract Traditional cancer treatments use nonspecific drugs and monoclonal antibodies to target tumor cells. Chimeric antigen receptor (CAR)-T cell therapy, however, leverages the immune system's T-cells recognize attack are isolated from patients modified tumor-associated antigens. CAR-T therapy has achieved FDA approval for treating blood cancers like B-cell acute lymphoblastic leukemia, large lymphoma, multiple myeloma by targeting CD-19 maturation Bi-specific chimeric receptors may contribute mitigating escape, but their efficacy could be limited in cases where certain cells do not express targeted Despite success cancers, technology faces challenges solid tumors, including lack of reliable antigens, hypoxic cores, immunosuppressive environments, enhanced reactive oxygen species, decreased T-cell infiltration. To overcome these challenges, current research aims identify antigens develop cost-effective, microenvironment-specific This review covers evolution against various hematological highlights faced suggests strategies obstacles, such as utilizing single-cell RNA sequencing artificial intelligence optimize clinical-grade

Language: Английский

Citations

102
Forks in the road for CAR T and CAR NK cell cancer therapies DOI
Oula K. Dagher, Avery D. Posey

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(12), P. 1994 - 2007

Published: Nov. 27, 2023

Language: Английский

Citations

56
Current challenges and therapeutic advances of CAR-T cell therapy for solid tumors DOI Creative Commons
T. R. Chen, Mingzhao Wang, Yanchao Chen

et al.

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: April 15, 2024

Abstract The application of chimeric antigen receptor (CAR) T cells in the management hematological malignancies has emerged as a noteworthy therapeutic breakthrough. Nevertheless, utilization and effectiveness CAR-T cell therapy solid tumors are still limited primarily because absence tumor-specific target antigen, existence immunosuppressive tumor microenvironment, restricted invasion proliferation, occurrence severe toxicity. This review explored history its latest advancements tumors. According to recent studies, optimizing design cells, implementing logic-gated refining delivery methods agents can all enhance efficacy therapy. Furthermore, combination shows promise way improve At present, numerous clinical trials involving for actively progress. In conclusion, both potential challenges when it comes treating As continues evolve, further innovations will be devised surmount associated with this treatment modality, ultimately leading enhanced response patients suffered

Language: Английский

Citations

32
The paradoxical role of cytokines and chemokines at the tumor microenvironment: a comprehensive review DOI Creative Commons
Toufik Abdul‐Rahman, Shankhaneel Ghosh, Sarah M. Badar

et al.

European journal of medical research, Journal Year: 2024, Volume and Issue: 29(1)

Published: Feb. 15, 2024

Abstract Tumor progression and eradication have long piqued the scientific community's interest. Recent discoveries about role of chemokines cytokines in these processes fueled renewed interest related research. These roles are frequently viewed as contentious due to their ability both suppress promote cancer progression. As a result, this review critically appraised existing literature discuss unique tumor microenvironment, well challenges future opportunities for exploiting develop novel targeted treatments. While modulatory molecules play an important suppression via enhanced cancer-cell identification by cytotoxic effector cells directly recruiting immunological stromal TME, we observed that they also proliferation. Many cytokines, including GM-CSF, IL-7, IL-12, IL-15, IL-18, IL-21, entered clinical trials people with advanced cancer, while FDA has approved interferon-alpha IL-2. Nonetheless, low efficacy dose-limiting toxicity limit agents' full potential. Conversely, Chemokines tremendous potential increasing immune-cell penetration microenvironment promoting beneficial interactions. When combined activate lymphocytes, producing IL-2, CD80, all which strong anticancer effect. This phenomenon opens door development effective combination therapies, such therapies can reverse escape, chemotaxis immunosuppressive like Tregs, MDSCs, TAMs.

Language: Английский

Citations

31
Neutrophils bearing adhesive polymer micropatches as a drug-free cancer immunotherapy DOI
Ninad Kumbhojkar, Supriya Prakash, Tatsuya Fukuta

et al.

Nature Biomedical Engineering, Journal Year: 2024, Volume and Issue: 8(5), P. 579 - 592

Published: Feb. 29, 2024

Language: Английский

Citations

29
Novel therapeutic agents in clinical trials: emerging approaches in cancer therapy DOI Creative Commons
Deepak Chandra Joshi, Anurag Sharma,

Sonima Prasad

et al.

Discover Oncology, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 11, 2024

Novel therapeutic agents in clinical trials offer a paradigm shift the approach to battling this prevalent and destructive disease, area of cancer therapy is on precipice trans formative revolution. Despite importance tried-and-true treatments like surgery, radiation, chemotherapy, disease continues evolve adapt, making new, more potent methods necessary. The field currently witnessing emergence wide range innovative approaches. Immunotherapy, including checkpoint inhibitors, CAR-T cell treatment, vaccines, utilizes host's immune system selectively target eradicate malignant cells while minimizing harm normal tissue. development targeted medicines kinase inhibitors monoclonal antibodies has allowed for less harmful approaches treating cancer. With help genomics molecular profiling, "precision medicine" customizes therapies each patient's unique genetic makeup maximize efficacy unwanted side effects. Epigenetic therapies, metabolic interventions, radio-pharmaceuticals, an increasing emphasis combination with synergistic effects further broaden landscape. Multiple-stage are essential determining safety these novel drugs, allowing patients gain access also furthering scientific understanding. future rife promise, as integration artificial intelligence big data potential revolutionize early detection prevention. Collaboration among researchers, healthcare providers, active involvement remain bedrock ongoing battle against In conclusion, dynamic evolving landscape provides hope improved treatment outcomes, emphasizing patient-centered, data-driven, ethically grounded we collectively strive towards cancer-free world.

Language: Английский

Citations

24
CAR‑T cell therapy: A breakthrough in traditional cancer treatment strategies (Review) DOI Creative Commons

Dahua Sun,

Xiang Shi, Sanyan Li

et al.

Molecular Medicine Reports, Journal Year: 2024, Volume and Issue: 29(3)

Published: Jan. 23, 2024

Chimeric antigen receptor (CAR)‑T cell therapy is an innovative approach to immune that works by modifying the T cells of a patient express CAR protein on their surface, and thus induce recognition destruction cancer cells. CAR‑T has shown some success in treating hematological tumors, but it still faces number challenges treatment solid such as selection, tolerability safety. In response these issues, studies continue improve design pursuit improved therapeutic efficacy future, expected become important treatment, may provide new ideas strategies for individualized immunotherapy. The present review provides comprehensive overview principles, clinical applications, therapy.

Language: Английский

Citations

18
Emerging roles of CAR-NK cell therapies in tumor immunotherapy: current status and future directions DOI Creative Commons

Yan Zhong,

Jingfeng Liu

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: July 10, 2024

Abstract Cancer immunotherapy harnesses the body’s immune system to combat malignancies, building upon an understanding of tumor immunosurveillance and evasion mechanisms. This therapeutic approach reactivates anti-tumor responses can be categorized into active, passive, combined immunization strategies. Active engages recognize attack cells by leveraging host immunity with cytokine supplementation or vaccination. Conversely, passive employs exogenous agents, such as monoclonal antibodies (anti-CTLA4, anti-PD1, anti-PD-L1) adoptive cell transfers (ACT) genetically engineered chimeric antigen receptor (CAR) T NK cells, exert effects. Over past decades, CAR-T therapies have gained significant traction in oncological treatment, offering hope through their targeted approach. However, potential adverse effects associated including release syndrome (CRS), off-tumor toxicity, neurotoxicity, warrant careful consideration. Recently, CAR-NK therapy has emerged a promising alternative landscape immunotherapy, distinguished its innate advantages over modalities. In this review, we will synthesize latest research clinical advancements therapies. We elucidate benefits employing oncology critically examine developmental bottlenecks impeding broader application. Our discussion aims provide comprehensive overview current status future cancer immunotherapy.

Language: Английский

Citations

18
Loading of CAR‐T cells with magnetic nanoparticles for controlled targeting suppresses inflammatory cytokine release and switches tumor cell death mechanism DOI Creative Commons
Felix Pfister,

Lucas R. Carnell,

L. Löffler

et al.

MedComm, Journal Year: 2025, Volume and Issue: 6(1)

Published: Jan. 1, 2025

Abstract Therapies against hematological malignancies using chimeric antigen receptors (CAR)‐T cells have shown great potential; however, therapeutic success in solid tumors has been constrained due to limited tumor trafficking and infiltration, as well the scarcity of cancer‐specific antigens. Therefore, enrichment tumor‐antigen specific CAR‐T desired region is critical for improving therapy efficacy reducing systemic on‐target/off‐tumor side effects. Here, we functionalized human with superparamagnetic iron oxide nanoparticles (SPIONs), making them magnetically controllable site‐directed targeting. SPION‐loaded maintained their cytolytic capacity melanoma expressing CAR‐specific chondroitin sulfate proteoglycan (CSPG4). Importantly, SPIONs suppressed cytokine release loaded cells, shifting cell death phenotype from pyroptosis apoptosis. Furthermore, could be enriched a dynamic flow model through an external magnetic field detected MRI. These results demonstrate that lytic cytotoxicity retained after SPION‐functionalization provides basis future site‐specific immunotherapies reduced adverse

Language: Английский

Citations

2
A Bibliometric and Knowledge-Map Analysis of CAR-T Cells From 2009 to 2021 DOI Creative Commons

Lele Miao,

Juan Zhang,

Zhengchao Zhang

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: March 18, 2022

Objectives A bibliometric and knowledge-map analysis is used to explore hotspots’ evolution development trends in the CAR-T cell field. By looking for research hotspots new topics, we can provide clues ideas researchers this Methods The articles reviews regarding cells were retrieved obtained from Web of Science Core Collection (WOSCC) on October 28th, 2021. CtieSpace [version 5.8.R3 (64-bit)] VOSviewer (version 1.6.17) conduct analysis. Results 660 authors 488 institutions 104 countries/regions published 6,867 papers 1,212 academic journals. United States was absolutely leading position institution that contributed most publications University Pennsylvania. Carl H June articles, while Shannon L Maude had co-citations. However, there little cooperation between countries. After 2012, among various also small. journals cell-related Frontiers immunology Cancers . Nevertheless, Blood New England Journal Medicine commonly co-cited influential hematological malignancies, related cytokine release syndrome (CRS), CD19, anti-tumor activity efficacy cells. latest topics included study solid tumors, universal cells, CAR-NK CD22, anakinra (the IL-1 receptor antagonist). tumors a rapidly developing hot Emerging field mainly glioblastoma (related targets: IL13Rα2, EGFRvIII, HER2), neuroblastoma target: GD2), sarcoma pancreatic cancer mesothelin), especially glioblastoma. Conclusion As an therapy with great potential clinical application prospects, still stage rapid development. will remain hotspot future.

Language: Английский

Citations

56