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

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

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Novel gene manipulation approaches to unlock the existing bottlenecks of CAR-NK cell therapy

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 11, 2025

Currently, CAR-T cell therapy is known as an efficacious treatment for patients with relapsed/refractory hematologic malignancies. Nonetheless, this method faces several bottlenecks, including low efficacy solid tumors, lethal adverse effects, high cost of autologous products, and the risk GvHD in allogeneic settings. As a potential alternative, CAR-NK can overcome most limitations provide off-the-shelf, safer, more affordable product. Although published results from preclinical clinical studies cells are promising, bottlenecks must be unlocked to maximize effectiveness therapy. These include vivo persistence, trafficking into tumor sites, modest sensitivity immunosuppressive microenvironment. In recent years, advances gene manipulation tools strategies have laid groundwork current This review will introduce existing discuss their advantages disadvantages. We also explore how these enhance therapy’s safety efficacy.

Language: Английский

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The next frontier in immunotherapy: potential and challenges of CAR-macrophages

Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)

Published: Aug. 5, 2024

Abstract Chimeric antigen receptor macrophage (CAR-MΦ) represents a significant advancement in immunotherapy, especially for treating solid tumors where traditional CAR-T therapies face limitations. CAR-MΦ offers promising approach to target and eradicate tumor cells by utilizing macrophages’ phagocytic antigen-presenting abilities. However, challenges such as the complex microenvironment (TME), variability expression, immune suppression limit their efficacy. This review addresses these issues, exploring mechanisms of action, optimal construct designs, interactions within TME. It also delves into ex vivo manufacturing CAR-MΦ, discussing autologous allogeneic sources importance stringent quality control. The potential synergies integrating with existing cancer like checkpoint inhibitors conventional chemotherapeutics are examined highlight possible enhanced treatment outcomes. Furthermore, regulatory pathways scrutinized alongside established protocols cells, identifying unique considerations essential clinical trials market approval. Proposed safety monitoring frameworks aim manage adverse events, cytokine release syndrome, crucial patient safety. Consolidating current research insights, this seeks refine therapeutic applications, overcome barriers, suggest future directions transition from experimental platforms standard care options.

Language: Английский

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Comprehensive snapshots of natural killer cells functions, signaling, molecular mechanisms and clinical utilization

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Nov. 8, 2024

Abstract Natural killer (NK) cells, initially identified for their rapid virus-infected and leukemia cell killing tumor destruction, are pivotal in immunity. They exhibit multifaceted roles cancer, viral infections, autoimmunity, pregnancy, wound healing, more. Derived from a common lymphoid progenitor, they lack CD3, B-cell, or T-cell receptors but wield high cytotoxicity via perforin granzymes. NK cells orchestrate immune responses, secreting inflammatory IFNγ immunosuppressive TGFβ IL-10. CD56 dim bright execute cytotoxicity, while also regulate However, beyond the dichotomy, detailed phenotypic diversity reveals many functional subsets that may not be optimal cancer immunotherapy. In this review, we provide comprehensive snapshots of cells’ functions states activation inhibitions angiogenesis, pregnancy fertility, aging, senescence mediated by complex signaling ligand-receptor interactions, including impact environment. As use engineered immunotherapy accelerates, often footsteps T-cell-derived engineering, examine interactions with other effectors relevant limitations microenvironment, intending to understand how enhance cytolytic activities specifically

Language: Английский

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Engineering innate immune cells for cancer immunotherapy

Nature Biotechnology, Journal Year: 2025, Volume and Issue: 43(4), P. 516 - 533

Published: April 1, 2025

Language: Английский

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Intratumoral Microbiota as a Target for Advanced Cancer Therapeutics

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(38)

Published: July 26, 2024

Abstract In recent years, advancements in microbial sequencing technology have sparked an increasing interest the bacteria residing within solid tumors and its distribution functions various tumors. Intratumoral critically modulate tumor oncogenesis development through DNA damage induction, chronic inflammation, epigenetic alterations, metabolic immune regulation, while also influencing cancer treatment efficacy by affecting drug metabolism. response to these discoveries, a variety of anti‐cancer therapies targeting microorganisms emerged. These approaches encompass oncolytic therapy utilizing tumor‐associated bacteria, design biomaterials based on intratumoral use bacterial components for delivery systems, comprehensive strategies aimed at eradication tumor‐promoting bacteria. Herein, this review article summarizes patterns different tumors, examines their impact evaluates current therapeutic centered Furthermore, challenges prospects developing drugs that target communities are explored, promising new directions treatment.

Language: Английский

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Advances in CAR-NK cell therapy for hematological malignancies

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: June 28, 2024

Chimeric antigen receptor T (CAR-T) cell therapy has revolutionized the treatment of hematological malignancies, demonstrably improving patient outcomes and prognosis. However, its application introduced new challenges, such as safety concerns, off-target toxicities, significant costs. Natural killer (NK) cells are crucial components innate immune system, capable eliminating tumor without prior exposure to specific antigens or pre-activation. This inherent advantage complements limitations cells, making CAR-NK a promising avenue for immunotherapy. In recent years, preclinical clinical studies have yielded preliminary evidence supporting efficacy in paving way future advancements review aims succinctly discuss characteristics, therapeutic progress, potential challenges associated with therapy.

Language: Английский

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Adoptive NK cell therapy in AML: progress and challenges

Clinical and Experimental Medicine, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 17, 2025

Adoptive cell therapy (ACT) using natural killer (NK) cells has emerged as a promising therapeutic strategy for acute myeloid leukemia (AML), addressing challenges such chemotherapy resistance and high relapse rates. Over the years, clinical trials studies have explored various sources of NK cells, including ex vivo expanded lines, CAR-NK peripheral blood-derived umbilical cord cells. These therapies demonstrated varying degrees efficacy, ranging from transient anti-leukemia activity to sustained remission in select patient groups. Toxicity profiles generally shown favorable safety outcomes, with minimal incidence severe adverse effects cytokine release syndrome (CRS) or graft-versus-host disease (GVHD). However, persistent remain, limited persistence, relapse, heterogeneity responses. This review provides comprehensive analysis outcomes toxicity provided trials, case reports conducted last 15 years judge on applicability ACT AML. Our highlights significant potential cell-based AML, while technical biological that must be overcome enhance their efficacy safety.

Language: Английский

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Implementation of chimeric antigen receptor (CAR) T-cell therapy in the NHS: prospects, promises and pitfalls

British Journal of Nursing, Journal Year: 2025, Volume and Issue: 34(5), P. S20 - S30

Published: March 6, 2025

The approval, introduction, and provision of chimeric antigen receptor (CAR) T-cell therapy in the UK NHS presents a innovative revolutionary approach cancer treatment management. CAR is highly specialised personalised type immunotherapy that involves reprogramming patient's immune system by synthetically modifying their T-cells to specifically target eliminate cells. This offers potential cure malignancies were previously deemed incurable or refractory conventional chemotherapy. therapy, however, associated with significant risks life-threatening complications, it entails substantial financial cost. implementation marks new era medicine, offering promising not only for improving outcomes, but enhancing survivorship quality life among patients advanced relapsing haematologic malignancies.

Language: Английский

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The Role of NK Cells in Cancer Immunotherapy: Mechanisms, Evasion Strategies, and Therapeutic Advances

Biomedicines, Journal Year: 2025, Volume and Issue: 13(4), P. 857 - 857

Published: April 2, 2025

Background/Objectives: Natural killer (NK) cells play a crucial role in tumor surveillance by exerting cytotoxic activity and modulating immune responses. However, tumors employ diverse evasion strategies that limit NK cell effectiveness. This review aims to explore the molecular mechanisms of activation inhibition cancer, influence microenvironment, latest advancements cell-based immunotherapies, including adoptive transfer Chimeric Antigen Receptor-Natural Killer (CAR-NK) therapies. Methods: A comprehensive literature was conducted, prioritizing peer-reviewed studies from last decade on biology, evasion, immunotherapeutic applications. The analysis includes data preclinical models clinical trials evaluating expansion strategies, cytokine-based stimulation, CAR-NK therapy developments. Results: eliminate through granule release, death receptor pathways, cytokine secretion. evade NK-mediated immunity downregulating activating ligands, secreting immunosuppressive molecules, altering microenvironment. Novel therapies, such as combination approaches with checkpoint inhibitors, enhance persistence therapeutic efficacy against both hematologic solid malignancies. Clinical suggest improved safety profiles compared CAR-T reduced release syndrome graft-versus-host disease. Conclusions: While immunotherapies hold great promise, challenges remain, limited tumor-induced immunosuppression. Addressing these hurdles will be critical for optimizing therapies advancing next-generation, off-the-shelf immunotherapeutics broader

Language: Английский

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