Breakthrough of solid tumor treatment: CAR-NK immunotherapy

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

Published: Jan. 20, 2024

Language: Английский

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TP53 Mutation-Mediated Immune Evasion in Cancer: Mechanisms and Therapeutic Implications

Cancers, Journal Year: 2024, Volume and Issue: 16(17), P. 3069 - 3069

Published: Sept. 3, 2024

Mutation in p53 is the most frequent event cancer development and a leading cause of therapy resistance due to evasion apoptosis cascade. Beyond chemotherapies radiation therapies, growing evidence indicates that p53-mutant tumors are resistant broad range immune-based such as immune checkpoint inhibitors, chimeric antigen receptor (CAR) T, hematopoietic stem cell transplantation (HSCT). This highlights role mutations driving tumor cells. In this review, we first summarize recent studies revealing mechanisms by which evade surveillance from T cells, natural killer (NK) macrophages. We then review how these mutant cells reshape microenvironment (TME), modulating bystander macrophages, neutrophils, regulatory (Treg) foster immunosuppression. Additionally, clinical observations indicative associated with loss or mutations. Finally, discuss therapeutic strategies enhance response wild-type (WT) tumors.

Language: Английский

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CAR-based immunotherapy for breast cancer: peculiarities, ongoing investigations, and future strategies

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

Published: April 12, 2024

Surgery, chemotherapy, and endocrine therapy have improved the overall survival postoperative recurrence rates of Luminal A, B, HER2-positive breast cancers but treatment modalities for triple-negative cancer (TNBC) with poor prognosis remain limited. The effective application rapidly developing chimeric antigen receptor (CAR)-T cell in hematological tumors provides new ideas cancer. Choosing suitable specific targets is crucial applying CAR-T treatment. In this paper, we summarize therapy’s potential different subtypes based on existing research progress, especially TNBC. CAR-based immunotherapy has resulted advancements CAR-macrophages, CAR-NK cells, CAR-mesenchymal stem cells (MSCs) may be more safer treating solid tumors, such as However, tumor microenvironment (TME) side effects pose challenges to immunotherapy. cells-derived exosomes are advantageous therapy. Exosomes carrying CAR immense value provide a modality good effects. review, an overview development discuss progress CAR-expressing We elaborate TNBC prospects using CAR-MSCs

Language: Английский

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Next‐generation chimeric antigen receptors for T‐ and natural killer‐cell therapies against cancer

Immunological Reviews, Journal Year: 2023, Volume and Issue: 320(1), P. 217 - 235

Published: Aug. 7, 2023

Adoptive cellular therapy using chimeric antigen receptor (CAR) T cells has led to a paradigm shift in the treatment of various hematologic malignancies. However, broad application this approach for myeloid malignancies and solid cancers been limited by paucity heterogeneity target expression, lack bona fide tumor-specific antigens that can be targeted without cross-reactivity against normal tissues. This may lead unwanted on-target off-tumor toxicities could undermine desired antitumor effect. Recent advances synthetic biology genetic engineering have enabled reprogramming immune effector enhance their selectivity toward tumors, thus mitigating adverse effects. In review, we outline current strategies being explored improve CAR tumor with focus on natural killer (NK) cells, progress made translating these clinic.

Language: Английский

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DNAM-1 chimeric receptor-engineered NK cells: a new frontier for CAR-NK cell-based immunotherapy

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: June 8, 2023

DNAM-1 is a major NK cell activating receptor and, together with NKG2D and NCRs, by binding specific ligands, strongly contributes to mediating the killing of tumor or virus-infected cells. specifically recognizes PVR Nectin-2 ligands that are expressed on some cells broad spectrum both hematological solid malignancies. So far, while engineered for different antigen chimeric receptors (CARs) have been extensively tested in preclinical clinical studies, use receptor-engineered has proposed only our recent proof-of-concept study deserves further development. The aim this perspective describe rationale using novel tool as new anti-cancer immunotherapy.

Language: Английский

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Bisphenol-A in Drinking Water Accelerates Mammary Cancerogenesis and Favors an Immunosuppressive Tumor Microenvironment in BALB–neuT Mice

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 6259 - 6259

Published: June 6, 2024

Bisphenol-A (BPA), a synthetic compound ubiquitously present in the environment, can act as an endocrine disruptor by binding to both canonical and non-canonical estrogen receptors (ERs). Exposure BPA has been linked various cancers, particular, those arising hormone-targeted tissues such breast. In this study, we evaluated effect of intake through drinking water on ErbB2/neu-driven cancerogenesis BALB–neuT mice, transgenic for mutated ErbB2/neu receptor gene, which reproducibly develop carcinomas all mammary glands. model, accelerated with increase number tumors per mouse concurrent decrease tumor-free overall survival. As assessed immunohistochemistry, were ER-negative but expressed high levels alternative GPR30, regardless exposure. On other hand, exposure resulted marked upregulation progesterone preinvasive Ki67, CD31, phosphorylated Akt invasive tumors. Moreover, based several infiltration markers immune cells, favored immunosuppressive tumor microenvironment. Finally, vitro cell survival studies performed line established from breast carcinoma confirmed that BPA’s impact cancer progression be particularly relevant after chronic, low-dose

Language: Английский

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Advancements in strategies for overcoming the blood–brain barrier to deliver brain-targeted drugs

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: Aug. 26, 2024

The blood-brain barrier is known to consist of a variety cells and complex inter-cellular junctions that protect the vulnerable brain from neurotoxic compounds; however, it also complicates pharmacological treatment central nervous system disorders as most drugs are unable penetrate on basis their own structural properties. This dramatically diminished therapeutic effect drug compromised its biosafety. In response, number often delivered lesions in invasive ways bypass obstruction barrier, such subdural administration, intrathecal convection-enhanced delivery. Nevertheless, these intrusive strategies introduce risk injury, limiting clinical application. recent years, intensive development nanomaterials science interdisciplinary convergence medical engineering have brought light penetration for brain-targeted drugs. this paper, we extensively discuss limitations delivery non-invasive nanomedicine disruption. meantime, analyze strengths provide outlooks further systems.

Language: Английский

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The emergence of DNAM-1 as the facilitator of NK cell-mediated killing in ovarian cancer

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

Published: Jan. 6, 2025

Ovarian cancer (OC) is the sixth most common malignancy in women and poor 5-year survival emphasises need for novel therapies. NK cells play an important role control of malignant disease but nature tumour-infiltrating peripheral OC remains unclear. Using flow cytometric analysis, we studied phenotype function blood, primary tumour metastatic tissue 80 with OC. The cell type contexture was explored utilising scRNAseq a focus on portraying immunogenic microenvironment determining characteristics dysfunctional population. proportion markedly elevated highly activated profile increased cytotoxicity. In contrast, numbers metastasis were substantially reduced, downregulation activatory receptors together PD-1 expression. scRNA-Seq identified 5 subpopulations along exhausted immature within compared to normal tissue. These features attenuated following chemotherapy where higher levels cytotoxic associated improved disease-free survival. Correlation clinical outcomes revealed high DNAM-1 expression tissue-localised be reduced Expression PVR, ligand, significantly tumours mediated lysis observed vitro. findings reveal profound modulation systemic which likely contributes rates local progression seen Immunotherapeutic approaches that overcome immune suppression enhance DNAM-1-targeted offer potential improve control.

Language: Английский

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A chimeric antigen receptor tailored to integrate complementary activation signals potentiates the antitumor activity of NK cells

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: March 6, 2025

Chimeric antigen receptors (CARs) are synthetic that reprogram the target specificity and functions of CAR-expressing effector cells. The design CAR constructs typically includes an extracellular antigen-binding moiety, hinge (H), transmembrane (TM), intracellular signaling domains. Conventional primarily designed for T cells but have been directly adopted other cells, including natural killer (NK) without tailored optimization. Given benefits CAR-NK over CAR-T in terms safety, off-the-shelf utility, escape, there is increasing emphasis on tailoring them to NK cell activation mechanisms. We first taken a stepwise approach modifying components such as combination order H, TM, domains achieve Functionality NK-tailored CARs were evaluated vitro vivo model CD19-expressing lymphoma, along with their expression properties found NK-CAR driven by synergistic NKG2D 2B4 rather than DNAM-1 induces potent Further, more effective CAR-mediated cytotoxicity was observed following sequential DAP10, not domain despite capacity TM recruit endogenous DAP10 signaling. Accordingly, incorporating 2B4, CD3ζ coupled CD8α H CD28 identified most promising candidate improve cytotoxicity. This provided antitumor activity conventional T-CAR when delivered both vivo. Hence, receptor-based hold great promise future potentially significant therapeutic benefits.

Language: Английский

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CD155 and Its Receptors as Targets for Cancer Therapy

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(16), P. 12958 - 12958

Published: Aug. 19, 2023

CD155, also known as the poliovirus receptor, is an adhesion molecule often overexpressed in tumors of different origins where it promotes cell migration and proliferation. In addition to this pro-tumorigenic function, CD155 plays immunomodulatory role during tumor progression since a ligand for both activating receptor DNAM-1 inhibitory TIGIT, expressed on cytotoxic innate adaptative lymphocytes. well-recognized involved anti-tumor immune surveillance. However, advanced stages, TIGIT up-regulated acts checkpoint counterbalancing DNAM-1-mediated cancer clearance. Pre-clinical studies have proposed direct targeting cells well enhancement functions promising therapeutic approaches. Moreover, immunotherapeutic use anti-TIGIT blocking antibody alone or combined therapy has already been included clinical trials. The aim review summarize all these potential therapies, highlighting still controversial progression.

Language: Английский

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