Current Perspectives on “Off-The-Shelf” Allogeneic NK and CAR-NK Cell Therapies

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Dec. 1, 2021

Natural killer cells (NK cells) are the first line of innate immune defense system, primarily located in peripheral circulation and lymphoid tissues. They kill virally infected malignant through a balancing play inhibitory stimulatory receptors. In pre-clinical investigational studies, NK show promising anti-tumor effects used adoptive transfer activated expanded cells, ex-vivo . express co-stimulatory molecules that attractive targets for immunotherapy cancers. Recent clinical trials investigating use CAR-NK different cancers to determine efficiency. Herein, we review cell therapy approaches preparation from tissue sources, ways expansion “off-the-shelf” allogeneic cell-doses therapies, how vector delivery systems engineer with CARs) cancer immunotherapy.

Language: Английский

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Heterogeneity of the tumor immune microenvironment and its clinical relevance

Experimental Hematology and Oncology, Journal Year: 2022, Volume and Issue: 11(1)

Published: April 23, 2022

During the course of tumorigenesis and subsequent metastasis, malignant cells gradually diversify become more heterogeneous. Consequently, tumor mass might be infiltrated by diverse immune-related components, including cytokine/chemokine environment, cytotoxic activity, or immunosuppressive elements. This immunological heterogeneity is universally presented spatially varies temporally along with evolution therapeutic intervention across almost all solid tumors. The anti-tumor immunity shows a profound association progression disease responsiveness to treatment, particularly in realm immunotherapy. Therefore, an accurate understanding essential for development effective therapies. Facilitated multi-regional -omics sequencing, single cell longitudinal liquid biopsy approaches, recent studies have demonstrated potential investigate complexity tumors its clinical relevance Here, we aimed review mechanism underlying immune microenvironment. We also explored how assessments facilitate personalized

Language: Английский

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γδ T cells: origin and fate, subsets, diseases and immunotherapy

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Nov. 22, 2023

The intricacy of diseases, shaped by intrinsic processes like immune system exhaustion and hyperactivation, highlights the potential renormalization as a promising strategy in disease treatment. In recent years, our primary focus has centered on γδ T cell-based immunotherapy, particularly pioneering use allogeneic Vδ2

Language: Английский

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Natural killer cells in clinical development as non-engineered, engineered, and combination therapies

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: Nov. 8, 2022

Natural killer (NK) cells are unique immune effectors able to kill cancer by direct recognition of surface ligands, without prior sensitization. Allogeneic NK transfer is a highly valuable treatment option for and has recently emerged with hundreds clinical trials paving the way finally achieve market authorization. Advantages cell therapies include use allogenic sources, off-the-shelf availability, no risk graft-versus-host disease (GvHD). have reached stage as ex vivo expanded differentiated non-engineered cells, chimeric antigen receptor (CAR)-engineered or CD16-engineered products, combination antibodies, priming agents, other drugs. This review summarizes recent status allogeneic cell-based hematological solid tumors, discussing main characteristics different sources used product development, their in manufacturing processes, engineering methods strategies adopted genetically modified chosen approaches therapies. A comparative analysis between NK-based non-engineered, engineered, presented, examining choices made developers regarding source targeted tumor indications, both cancers. Clinical trial outcomes discussed and, when available, assessed comparison preclinical data. Regulatory challenges approval reviewed, highlighting lack specificity requirements standardization products. Additionally, competitive landscape business field presented. offers comprehensive overview effort driven biotech pharmaceutical companies academic centers bring pivotal stages

Language: Английский

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Exploiting innate immunity for cancer immunotherapy

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Nov. 27, 2023

Abstract Immunotherapies have revolutionized the treatment paradigms of various types cancers. However, most these immunomodulatory strategies focus on harnessing adaptive immunity, mainly by inhibiting immunosuppressive signaling with immune checkpoint blockade, or enhancing immunostimulatory bispecific T cell engager and chimeric antigen receptor (CAR)-T cell. Although agents already achieved great success, only a tiny percentage patients could benefit from immunotherapies. Actually, immunotherapy efficacy is determined multiple components in tumor microenvironment beyond immunity. Cells innate arm system, such as macrophages, dendritic cells, myeloid-derived suppressor neutrophils, natural killer unconventional also participate cancer evasion surveillance. Considering that cornerstone antitumor response, utilizing immunity provides potential therapeutic options for control. Up to now, exploiting agonists stimulator interferon genes, CAR-macrophage -natural therapies, metabolic regulators, novel exhibited potent activities preclinical clinical studies. Here, we summarize latest insights into roles cells discuss advances arm-targeted strategies.

Language: Английский

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Immunotherapy in hematologic malignancies: achievements, challenges and future prospects

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Aug. 18, 2023

Abstract The immune-cell origin of hematologic malignancies provides a unique avenue for the understanding both mechanisms immune responsiveness and escape, which has accelerated progress immunotherapy. Several categories immunotherapies have been developed are being further evaluated in clinical trials treatment blood cancers, including stem cell transplantation, checkpoint inhibitors, antigen-targeted antibodies, antibody-drug conjugates, tumor vaccines, adoptive therapies. These shown potential to induce long-term remission refractory or relapsed patients led paradigm shift cancer with great success. Different immunotherapeutic approaches their advantages but also shortcomings that need be addressed. To provide clinicians timely information on these revolutionary therapeutic approaches, comprehensive review historical perspectives applications considerations Here, we first outline recent advances made various malignancies. We discuss specific action, summarize outcomes malignancies, as well adverse effects toxicity management then novel insights into challenges future directions.

Language: Английский

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The Function of NK Cells in Tumor Metastasis and NK Cell-Based Immunotherapy

Cancers, Journal Year: 2023, Volume and Issue: 15(8), P. 2323 - 2323

Published: April 16, 2023

Metastatic tumors cause the most deaths in cancer patients. Treating metastasis remains primary goal of current research. Although immune system prevents and kills tumor cells, function metastatic has been unappreciated for decades because are able to develop complex signaling pathways suppress responses, leading them escape detection elimination. Studies showed NK cell-based therapies have many advantages promise fighting cancers. We here review progression, specifically focusing on ability cells antimetastasis, how cell attack, as well recent development effective antimetastatic immunotherapies.

Language: Английский

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Recent Advances in CAR-Based Solid Tumor Immunotherapy

Cells, Journal Year: 2023, Volume and Issue: 12(12), P. 1606 - 1606

Published: June 11, 2023

Adoptive cell therapy using chimeric antigen receptor (CAR) technology is one of the most advanced engineering platforms for cancer immunotherapy. CAR-T cells have shown remarkable efficacy in treatment hematological malignancies. However, their limitations solid tumors include an immunosuppressive tumor microenvironment (TME), insufficient infiltration, toxicity, and absence tumor-specific antigens. Although recent advances design-such as incorporation co-stimulatory domains development armored cells-have promising results treating tumors, there are still challenges that need to be addressed. To overcome these limitations, other immune cells, such natural killer (NK) macrophages (M), been developed attractive options efficient immunotherapy tumors. CAR-NK exhibit substantial clinical improvements with "off-the-shelf" availability low toxicity. CAR-M therapeutic potential because can infiltrate TME Here, we review future perspectives associated engineered cell-based immunotherapies We also summarize ongoing trials investigating safety CAR-T, CAR-NK, CAR-M, targeting

Language: Английский

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Synapse-tuned CARs enhance immune cell anti-tumor activity

Nature Biotechnology, Journal Year: 2023, Volume and Issue: 41(10), P. 1434 - 1445

Published: Feb. 2, 2023

Language: Английский

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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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