CAR-macrophage: Breaking new ground in cellular immunotherapy

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

Published: Oct. 3, 2024

Chimeric Antigen Receptor (CAR) technology has revolutionized cellular immunotherapy, particularly with the success of CAR-T cells in treating hematologic malignancies. However, have limited efficacy against solid tumors. To address these limitations, CAR-macrophages (CAR-Ms) leverage innate properties macrophages specificity and potency CAR technology, offering a novel promising approach to cancer immunotherapy. Preclinical studies shown that CAR-Ms can effectively target destroy tumor cells, even within challenging microenvironments, by exhibiting direct cytotoxicity enhancing recruitment activation other immune cells. Additionally, favorable safety profile their persistence tumors position as potentially safer more durable therapeutic options compared This review explores recent advancements including engineering strategies optimize anti-tumor preclinical evidence supporting use. We also discuss challenges future directions developing therapies, emphasizing potential revolutionize By harnessing unique macrophages, offer groundbreaking overcoming current limitations cell paving way for effective sustainable treatments.

Language: Английский

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Tumor Microenvironment: Cellular Interaction and Metabolic Adaptations

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3642 - 3642

Published: March 25, 2024

The tumor microenvironment (TME) plays a critical role in cancerogenesis [...]

Language: Английский

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CAR-NK cells for gastrointestinal cancer immunotherapy: from bench to bedside

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Oct. 23, 2024

Gastrointestinal (GI) cancers represent a significant health burden worldwide. Their incidence continues to increase, and their management remains clinical challenge. Chimeric antigen receptor (CAR) natural killer (NK) cells have emerged as promising alternative CAR-T for immunotherapy of GI cancers. Notably, CAR-NK offer several advantages, including reduced risk graft-versus-host disease, lower cytokine release syndrome, the ability target cancer through both CAR-dependent cytotoxic mechanisms. This review comprehensively discusses development applications in treatment We explored various sources NK cells, CAR design strategies, current state cell therapy cancers, highlighting recent preclinical trials. Additionally, we addressed existing challenges propose potential strategies enhance efficacy safety therapy. Our findings highlight revolutionize pave way future applications.

Language: Английский

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Research Progress of NK Cells in Glioblastoma Treatment

OncoTargets and Therapy, Journal Year: 2025, Volume and Issue: Volume 18, P. 87 - 106

Published: Jan. 1, 2025

NK cells are a type of antitumor immune cell with promising clinical application, following T cells. The activity is primarily regulated by their surface receptors and microenvironment. In gliomas, the tumor microenvironment exerts strong immunosuppressive effect, which significantly reduces efficacy immunotherapy. Therefore, this review aims to discuss latest research on role in glioma immunotherapy, focusing aspects such as development, function, localization. It summarizes information compounds, monoclonal antibodies, cytokine therapies targeting while emphasizing current status trends gene-modified treatment. Additionally, it explores molecular mechanisms underlying escape cells, providing theoretical foundation new perspectives for cell-based immunotherapy gliomas.

Language: Английский

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NK cells in renal cell carcinoma and its implications for CAR-NK therapy

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: Feb. 20, 2025

Renal cell carcinoma (RCC) is a malignancy that makes up 3% of adult cancers and 20%-30% patients were diagnosed with metastatic RCC in the beginning, while median overall survival (OS) systemic therapy ranges from 16 months to 50 months. Immunotherapy, novel relies on specific binding immune cells tumor cells, may be potential for advanced renal carcinoma. While chimeric antigen receptor NK-cell (CAR-NK) has been investigated variety solid tumors, research its application also reported by several teams. In this review, we introduced cytotoxicity mechanisms NK summarized connections between posted new insights into CAR-NK therapy. To date, most researches focusing only claimed suppression even escape, yet molecules involved could interesting targets

Language: Английский

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New player in CAR-T manufacture field: comparison of umbilical cord to peripheral blood strategies

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 21, 2025

One of the most successful treatments in hematologic cancer is chimeric antigen receptor (CAR)-T cell-based immunotherapy. However, CAR-T therapy not without challenges like costly manufacturing process required to personalize each treatment for individual patients or graft-versus-host disease. Umbilical cord blood (UCB) has been commonly used hematopoietic cell transplant as it offers several advantages, including its rich source stem cells, lower risk disease, and easier matching recipients due less stringent HLA requirements compared bone marrow peripheral cells. In this review, we have discussed advantages disadvantages different strategies with use allogeneic autologous We compare them UCB approach discuss ongoing pre-clinical clinical trials field. Finally, propose a bank readily available

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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CAR-NK cell therapy: promise and challenges in solid tumors

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 7, 2025

Over the past few years, cellular immunotherapy has emerged as a promising treatment for certain hematologic cancers, with various CAR-T therapies now widely used in clinical settings. However, challenges related to production of autologous cell products and management toxicity highlight need new therapy options that are universal, safe, effective. Natural killer (NK) cells, which part innate immune system, offer unique advantages, including potential off-the-shelf therapy. A recent first-in-human trial CD19-CAR-NK infusion patients relapsed/refractory lymphoid malignancies demonstrated safety activity. Building on these positive outcomes, current research focuses enhancing CAR-NK potency by increasing their vivo persistence addressing functional exhaustion. There is also growing interest applying successes seen solid tumors. This review discusses trends emerging concepts engineering next-generation CAR- NK therapies. It will cover process constructing targets manufacturing, role Additionally, it examine mechanisms action status tumors, along limitations, future challenges. The insights provided may guide investigations aimed at optimizing broader range malignancies.

Language: Английский

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Cell-based immunotherapies for solid tumors: advances, challenges, and future directions

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: April 28, 2025

Cell-based immunotherapies, including CAR-T, CAR-NK, and TCR-T therapies, represent a transformative approach to cancer treatment by offering precise targeting of tumor cells. Despite their success in hematologic malignancies, these therapies encounter significant challenges treating solid tumors, such as antigen heterogeneity, immunosuppressive microenvironments, limited cellular infiltration, off-target toxicity, difficulties manufacturing scalability. CAR-T cells have demonstrated exceptional efficacy blood cancers but face obstacles whereas CAR-NK offer reduced graft-versus-host disease similar barriers. expand the range treatable intracellular antigens require meticulous selection prevent effects. Alternative like TIL, NK, CIK show promise further optimization enhance persistence overcome Manufacturing complexity, high costs, ensuring safety remain critical challenges. Future advancements gene editing, multi-antigen targeting, synthetic biology, off-the-shelf products, personalized medicine hold potential address issues use cell-based therapies. Continued research innovation are essential improving safety, efficacy, scalability, ultimately leading better patient outcomes.

Language: Английский

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Harnessing the Power of NK Cell Receptor Engineering as a New Prospect in Cancer Immunotherapy

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(9), P. 1143 - 1143

Published: Aug. 29, 2024

Natural killer (NK) cells have recently gained popularity as an alternative for cancer immunotherapy. Adoptive cell transfer employing NK offers a safer therapeutic option compared to T-cell-based therapies, due their significantly lower toxicity and the availability of diverse autologous allogeneic sources. However, several challenges are associated with including limited in vivo persistence, immunosuppressive hostile tumor microenvironment (TME), lack effective treatments solid tumors. To address these limitations, modification stably produce cytokines has been proposed strategy enhance persistence proliferation. Additionally, overexpression activating receptors blockade inhibitory can restore functions hindered by TME. further improve infiltration elimination tumors, innovative approaches focusing on enhancement chemotaxis through chemotactic introduced. This review highlights latest advancements preclinical clinical studies investigating engineering activating, inhibitory, receptors; discusses recent progress cytokine manipulation; explores potential combining chimeric antigen receptor (CAR) technology engineering.

Language: Английский

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