Targeting immunogenic cell stress and death for cancer therapy

Nature Reviews Drug Discovery, Journal Year: 2024, Volume and Issue: 23(6), P. 445 - 460

Published: April 15, 2024

Language: Английский

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Challenges and new technologies in adoptive cell therapy

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: Aug. 18, 2023

Abstract Adoptive cell therapies (ACTs) have existed for decades. From the initial infusion of tumor-infiltrating lymphocytes to subsequent specific enhanced T receptor (TCR)-T and chimeric antigen (CAR)-T therapies, many novel strategies cancer treatment been developed. Owing its promising outcomes, CAR-T therapy has revolutionized field ACTs, particularly hematologic malignancies. Despite these advances, still limitations in both autologous allogeneic settings, including practicality toxicity issues. To overcome challenges, researchers focused on application CAR engineering technology other types immune engineering. Consequently, several new based developed, CAR-NK, CAR-macrophage, CAR-γδT, CAR-NKT. In this review, we describe development, advantages, possible challenges aforementioned ACTs discuss current aimed at maximizing therapeutic potential ACTs. We also provide an overview various gene transduction employed immunotherapy given their importance Furthermore, possibility that capable creating a positive feedback circuit, as healthy systems do, could address flaw single type ACT, thus serve key players future immunotherapy.

Language: Английский

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Tumor microenvironment targeted nano-drug delivery systems for multidrug resistant tumor therapy

Theranostics, Journal Year: 2025, Volume and Issue: 15(5), P. 1689 - 1714

Published: Jan. 2, 2025

In recent years, nano-drug delivery systems (Nano-DDS) that target the tumor microenvironment (TME) to overcome multidrug resistance (MDR) have become a research hotspot in field of cancer therapy. By precisely targeting TME and regulating its unique pathological features, such as hypoxia, weakly acidic pH, abnormally expressed proteins, etc., these Nano-DDS enable effective therapeutic agents reversal MDR. This scientific community is increasing investment development diversified exploring their anti-drug potential. Therefore, it particularly important conduct comprehensive review progress TME-targeted years. After brief introduction MDR, design principle structure liposomes, polymer micelles inorganic nanocarriers are focused on, characteristics described. It also demonstrates how break through MDR treatment various mechanisms, discusses synthetic innovation, results overcoming mechanisms. The was concluded with deliberations on key challenges future outlooks

Language: Английский

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Chimeric antigen receptor engineered natural killer cells for cancer therapy

Experimental Hematology and Oncology, Journal Year: 2023, Volume and Issue: 12(1)

Published: Aug. 10, 2023

Abstract Natural killer (NK) cells, a unique component of the innate immune system, are inherent killers stressed and transformed cells. Based on their potent capacity to kill cancer cells good tolerance healthy NK have been successfully employed in adoptive cell therapy treat patients. In recent years, clinical success chimeric antigen receptor (CAR)-T has proven vast potential gene-manipulated as main force fight cancer. Following lessons learned from mature gene-transfer technologies advanced strategies CAR-T therapy, rapidly explored promising candidate for CAR-based therapy. An exponentially growing number studies multiple sources CAR-NK target wide range cancer-related antigens, showing remarkable outcomes encouraging safety profiles. Clinical trials also shown impressive therapeutic efficacy treatment hematological tumors, but solid tumors is still initial stages. this review, we present favorable profile platform engineering then summarize therapies up-to-date preclinical investigations. Finally, evaluate challenges remaining describe existing that can assist us devising future prospective solutions.

Language: Английский

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T cell-derived exosomes in tumor immune modulation and immunotherapy

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

Published: April 20, 2023

Exosomes are nanoscale vesicles secreted by most cells and have a phospholipid bilayer structure. contain DNA, small RNA, proteins, other substances that can carry proteins nucleic acids participate in communication between cells. T an indispensable part of adaptive immunity, the functions cell-derived exosomes been widely studied. In more than three decades since discovery exosomes, several studies revealed play novel role cell-to-cell signaling, especially tumor immune response. this review, we discuss function derived from different cell subsets, explore applications immunotherapy, consider associated challenges.

Language: Английский

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Immune regulatory genes impact the hot/cold tumor microenvironment, affecting cancer treatment and patient outcomes

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

Published: Jan. 22, 2025

Background and aims Immunologically hot tumors, characterized by an inflamed tumor microenvironment (TME), contrast significantly with immunologically cold tumors. The identification of these immune subtypes holds clinical significance, as tumors may exhibit improved prognoses heightened responsiveness to checkpoint blockade therapy. Nevertheless, yet there is no consensus regarding the clinically relevant definition hot/cold influence genes on formation remains poorly understood. Methods Data for 33 different types cancer were obtained from Cancer Genome Atlas database, their composition was assessed using CIBERSORT algorithm. Tumors categorized either or based distinct composition, ongoing response, overall survival. A customized immunogram created identify important immunological characteristics. Kyoto Encyclopedia Genes Genomes Hallmark pathway enrichment evaluated through gene set variation analysis. Additionally, hub that regulate identified, expression patterns analyzed single-cell RNA sequencing. Furthermore, drug sensitivity molecular docking analyses performed potential candidates capable transforming into For validation, a cohort patients diagnosed pancreatic adenocarcinoma examined multiplex immunohistochemistry. Results We able differentiate between in various (bladder urothelial carcinoma, adenocarcinoma, cervical squamous cell carcinoma) analyzing presence CD8+ T cells, activated natural killer M2-type macrophages, well cytolytic activity proliferation. Hub TME, including PDCD1 , CD276 NT5E discovered. increased its prognostic significance confirmed immunohistochemistry adenocarcinoma. Finally, dasatinib tozasertib identified converting Conclusion In this study, we developed framework discerning significant across types, further identifying several targets enhance anticancer treatment efficacy.

Language: Английский

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Intracellular and extracellular activities of V-domain Ig-containing suppressor of T cell activation (VISTA) modulated by immunosuppressive factors of tumour microenvironment

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217581 - 217581

Published: Feb. 1, 2025

V-domain Ig-containing suppressor of T cell activation (VISTA) is a unique immune checkpoint protein, which was reported to display both receptor and ligand activities. However, the mechanisms regulation VISTA activity functions by factors tumour microenvironment (TME) remain unclear understanding these processes required in order develop successful personalised cancer immunotherapeutic strategies approaches. Here we report for very first time that interacts with another protein galectin-9 inside most likely facilitating its interaction TGF-β-activated kinase 1 (TAK1). This process protection lysosomes, crucial many types tissues. We found expression can be differentially controlled present TME, such as transforming growth factor beta type (TGF-β) hypoxia well other activating hypoxic signalling. confirmed involvement important pathways modulated TME influences different types. These networks include: TGF-β-Smad3 pathway, TAK1 (TGF-β-activated 1) or apoptosis signal-regulating (ASK1)-induced transcription 2 (ATF-2) signalling pathway. Based on this work determined five critical role controlling (modulating downregulating) expression.

Language: Английский

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Living Bacteria: A New Vehicle for Vaccine Delivery in Cancer Immunotherapy

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2056 - 2056

Published: Feb. 26, 2025

Cancer vaccines, aimed at evolving the human immune system to eliminate tumor cells, have long been explored as a method of cancer treatment with significant clinical potential. Traditional delivery systems face challenges in directly targeting cells and delivering adequate amounts antigen due hostile microenvironment. Emerging evidence suggests that certain bacteria naturally home on tumors modulate antitumor immunity, making bacterial vectors promising vehicle for precision vaccines. Live vehicles offer several advantages, including colonization, precise drug delivery, stimulation, them compelling option immunotherapy. In this review, we explore mechanisms action behind living bacteria-based recent progress popular chassis, strategies specific payload biocontainment ensure safety. These approaches will lay foundation developing an affordable, widely applicable vaccine system. This review also discusses future opportunities harnessing bacterial-based vaccines enhanced therapeutic outcomes treatment.

Language: Английский

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Targeting Immune Checkpoint Inhibitors for Non-Small-Cell Lung Cancer: Beyond PD-1/PD-L1 Monoclonal Antibodies

Cancers, Journal Year: 2025, Volume and Issue: 17(5), P. 906 - 906

Published: March 6, 2025

Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide. Immunotherapy targeting the PD-1/PD-L1 axis has revolutionized treatment, providing durable responses in subset patients. However, with fewer than 50% patients achieving significant benefits, there is critical need to expand therapeutic strategies. This review explores emerging targets immune checkpoint inhibition beyond PD-1/PD-L1, including CTLA-4, TIGIT, LAG-3, TIM-3, NKG2A, and CD39/CD73. We highlight biological basis CD8 T cell exhaustion shaping antitumor response. Novel approaches additional inhibitory receptors (IR) are discussed, focus on their distinct mechanisms action combinatory potential existing therapies. Despite advancements, challenges remain overcoming resistance optimizing patient selection. underscores importance dual blockade innovative bispecific antibody engineering maximize outcomes for NSCLC

Language: Английский

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Progresses in biomarkers for cancer immunotherapy

MedComm, Journal Year: 2023, Volume and Issue: 4(5)

Published: Oct. 1, 2023

Currently, checkpoint inhibitor-based immunotherapy has emerged as prevailing treatment modality for diverse cancers. However, a first-line therapy not consistently yielded durable responses. Moreover, the risk of immune-related adverse events increases with combination regimens. Thus, development predictive biomarkers is needed to optimize individuals benefit, minimize toxicities, and guide approaches. The greatest focus been on tumor programmed cell death-ligand 1 (PD-L1), microsatellite instability (MSI), mutational burden (TMB). there remains subject debate due thresholds variability significant heterogeneity. Major unmet challenges in are discovery validation biomarkers. Here, we show status PD-L1, MSI, TMB, emerging data novel biomarker strategies oncogenic signaling epigenetic regulation. Considering exploration peripheral intestinal immunity served noninvasive alternative predicting immunotherapy, this review also summarizes current systemic immunity, encompassing solute PD-L1 circulating DNA infiltrating lymphocytes, routine inflammatory markers cytokines, well gut microbiota. This provides up-to-date information evolving field currently available immunotherapy. Future warranted.

Language: Английский

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