Alendronate Triggered Dual‐Cascade Targeting Prodrug Nanoparticles for Enhanced Tumor Penetration and STING Activation of Osteosarcoma DOI Open Access

Meifang Shen,

Yushu Wang,

Tiejun Bing

и другие.

Advanced Functional Materials, Год журнала: 2023, Номер 33(49)

Опубликована: Сен. 3, 2023

Abstract The complex physiological environment in bone tissue poses a challenge to the efficient delivery of chemotherapeutic agents for osteosarcoma (OS) treatment; hence, an drug system designed OS is highly desired. Herein, alendronate (Ale)‐based cationic platinum prodrug nanoparticles (Ale NP) are developed, which exhibit cascade responsiveness tumor microenvironment. With Ale triggered targeting and charge reversal effects, NP demonstrates superior capacity achieving deep penetration into dense tissues. Furthermore, can induce dendritic cell (DC) maturation via activation cyclic GMP‐AMP synthase‐stimulator interferon genes (cGAS‐STING) pathway using drugs. potent phenanthridine (Pt(II)) be released presence overexpressed glutathione (GSH) cells, thereby dual‐targeted drugs OS. Notably, not only effectively eliminates internal region but also acts as STING agonist reverse suppressive microenvironment Overall, Ale‐triggered dual‐cascade significantly improve OS, hence paving promising avenue clinical treatment

Язык: Английский

CD8 T-cell subsets: heterogeneity, functions, and therapeutic potential DOI Creative Commons
Choong‐Hyun Koh, Suyoung Lee,

Minkyeong Kwak

и другие.

Experimental & Molecular Medicine, Год журнала: 2023, Номер 55(11), С. 2287 - 2299

Опубликована: Ноя. 1, 2023

Abstract CD8 T cells play crucial roles in immune surveillance and defense against infections cancer. After encountering antigenic stimulation, naïve differentiate acquire effector functions, enabling them to eliminate infected or malignant cells. Traditionally, cytotoxic cells, characterized by their ability produce cytokines release granules directly kill target have been recognized as the constituents of predominant T-cell subset. However, emerging evidence suggests distinct subsets that each exhibit unique functions therapeutic potential. This review highlights recent advancements our understanding contributions these various disease pathologies. Understanding diverse is discern complex dynamics responses different settings. Furthermore, development immunotherapeutic approaches specifically regulate function holds great promise for precision medicine.

Язык: Английский

Процитировано

115
Tumour circular RNAs elicit anti-tumour immunity by encoding cryptic peptides DOI
Di Huang, Xiao‐Feng Zhu, Shuying Ye

и другие.

Nature, Год журнала: 2023, Номер 625(7995), С. 593 - 602

Опубликована: Дек. 13, 2023

Язык: Английский

Процитировано

95
Reactive oxygen species-powered cancer immunotherapy: Current status and challenges DOI

Mengying He,

Mengyuan Wang,

Tao Xu

и другие.

Journal of Controlled Release, Год журнала: 2023, Номер 356, С. 623 - 648

Опубликована: Март 21, 2023

Язык: Английский

Процитировано

92
Photon-Controlled Pyroptosis Activation (PhotoPyro): An Emerging Trigger for Antitumor Immune Response DOI
Mingle Li, Jungryun Kim, Hyeonji Rha

и другие.

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(11), С. 6007 - 6023

Опубликована: Март 7, 2023

Pyroptosis refers to the process of gasdermin-mediated lytic programmed cell death (PCD) characterized by release pro-inflammatory cytokines. Our knowledge pyroptosis has expanded beyond cellular level and now includes extracellular responses. In recent years, attracted considerable attention due its potential induce host immunity. For instance, at 2022 International Medicinal Chemistry Natural Active Ligand Metal-Based Drugs (MCNALMD) conference, numerous researchers demonstrated an interest in photon-controlled activation ("PhotoPyro"), emerging pyroptosis-engineered approach for activating systemic immunity via photoirradiation. Given this enthusiasm, we share Perspective our views on area expound how why "PhotoPyro" could trigger antitumor (i.e., turning so-called "cold" tumors "hot"). doing so, have tried highlight cutting-edge breakthroughs PhotoPyro while suggesting areas future contributions. By providing insights into current state art serving as a resource individuals interested working area, it is hoped that will set stage evolve broadly applicable cancer treatment strategy.

Язык: Английский

Процитировано

91
Cold and hot tumors: from molecular mechanisms to targeted therapy DOI Creative Commons
Bo Wu, Bo Zhang, Bowen Li

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Окт. 18, 2024

Immunotherapy has made significant strides in cancer treatment, particularly through immune checkpoint blockade (ICB), which shown notable clinical benefits across various tumor types. Despite the transformative impact of ICB treatment therapy, only a minority patients exhibit positive response to it. In with solid tumors, those who respond well typically demonstrate an active profile referred as "hot" (immune-inflamed) phenotype. On other hand, non-responsive may distinct "cold" (immune-desert) phenotype, differing from features tumors. Additionally, there is more nuanced "excluded" positioned between and categories, known type. Effective differentiation understanding intrinsic factors, characteristics, TME, external factors are critical for predicting results. It widely accepted that therapy exerts profound effect on limited efficacy against or "altered" necessitating combinations therapeutic modalities enhance cell infiltration into tissue convert tumors ones. Therefore, aligning traits this review systematically delineates respective influencing extensively discusses varied approaches drug targets based assess efficacy.

Язык: Английский

Процитировано

60
Synergistic efficacy of simultaneous anti-TGF-β/VEGF bispecific antibody and PD-1 blockade in cancer therapy DOI Creative Commons

Mengke Niu,

Ming Yi, Yuze Wu

и другие.

Journal of Hematology & Oncology, Год журнала: 2023, Номер 16(1)

Опубликована: Авг. 12, 2023

Recently, therapeutic antibodies against programmed cell death 1 (PD-1) and its ligand (PD-L1) have exerted potent anticancer effect in a variety of tumors. However, blocking the PD-1/PD-L1 axis alone is not sufficient to restore normal immune response. Other negative regulators antitumor immunity, like TGF-β VEGFA, are also involved escape tumor cells induce immunotherapy resistance.We developed novel anti-TGF-β/VEGF bispecific antibody Y332D based on Nano-YBODY™ technology platform. The CCK-8, flow cytometry, SBE4 luciferase reporter assay, western blotting transwell assays were used measure biological activities anti-TGF-β moiety. NFAT luminescent viability assay tube formation anti-VEGF vivo efficacy or combination with PD-1 blockade was evaluated H22, EMT-6, 4T1, AKT/Ras-driven murine hepatocellular carcinoma models. Immunofluorescent staining, RNA-seq quantitative RT-PCR adopted analyze alterations microenvironment.Y332D could maintain specific binding affinities for VEGFA. almost entirely counteracted vitro functions including immunosuppression, activated signaling, epithelial-mesenchymal transition (EMT), VEGF/VEGFR HUVEC proliferation formation. experiment data demonstrated that more effective inhibiting growth metastasis than monotherapies. In therapies, plus exhibited most durable effect. Mechanistically, upregulated density function tumor-infiltrating lymphocytes reinvigorated immunity.Y332D simultaneously block VEGF signalings. comparison monotherapies, combined exerts superior through improving microenvironment.

Язык: Английский

Процитировано

53
Medicinal plant-derived mtDNA via nanovesicles induces the cGAS-STING pathway to remold tumor-associated macrophages for tumor regression DOI Creative Commons
Jinfeng Liu,

Jiaxin Xiang,

Cuiyuan Jin

и другие.

Journal of Nanobiotechnology, Год журнала: 2023, Номер 21(1)

Опубликована: Март 6, 2023

Plant-derived nanovesicles (PDNVs) have been proposed as a major mechanism for the inter-kingdom interaction and communication, but effector components enclosed in vesicles mechanisms involved are largely unknown. The plant Artemisia annua is known an anti-malaria agent that also exhibits wide range of biological activities including immunoregulatory anti-tumor properties with to be further addressed. Here, we isolated purified exosome-like particles from A. annua, which were characterized by nano-scaled membrane-bound shape hence termed artemisia-derived (ADNVs). Remarkably, demonstrated inhibit tumor growth boost immunity mouse model lung cancer, primarily through remolding microenvironment reprogramming tumor-associated macrophages (TAMs). We identified plant-derived mitochondrial DNA (mtDNA), upon internalized into TAMs via vesicles, molecule induce cGAS-STING pathway driving shift pro-tumor phenotype. Furthermore, our data showed administration ADNVs greatly improved efficacy PD-L1 inhibitor, prototypic immune checkpoint tumor-bearing mice. Together, present study, first time, knowledge, unravels wherein medical mtDNA, nanovesicles, induces immunostimulatory signaling mammalian cells resetting promoting eradication.

Язык: Английский

Процитировано

52
Cuproptosis-immunotherapy using PD-1 overexpressing T cell membrane-coated nanosheets efficiently treats tumor DOI
Tiantian Liu, Zehang Zhou, Mengxing Zhang

и другие.

Journal of Controlled Release, Год журнала: 2023, Номер 362, С. 502 - 512

Опубликована: Сен. 9, 2023

Язык: Английский

Процитировано

49
Neoadjuvant adebrelimab in locally advanced resectable esophageal squamous cell carcinoma: a phase 1b trial DOI Creative Commons
Jun Yin, Jingnan Yuan, Yunjin Li

и другие.

Nature Medicine, Год журнала: 2023, Номер 29(8), С. 2068 - 2078

Опубликована: Июль 24, 2023

Abstract Overall survival (OS) benefits of neoadjuvant immunotherapy remain elusive in locally advanced esophageal squamous cell carcinomas (ESCC). Here, we reported the results a phase 1b trial PD-L1 blockade with adebrelimab resectable ESCC. Patients received two doses followed by surgery. The primary endpoints were safety and feasibility; secondary included pathologic complete response (pCR) OS. Our data showed feasibility had been met. Common treatment-related adverse events anorexia (32%) fatigue (16%), without grade 3 or more events. Of 30 patients enrolled trial, 25 underwent successful resection surgery delay 24% major responses including pCR rate 8%. 2-year OS was 92%. Responsive an immune-enriched tumor microenvironment phenotype, whereas nonresponsive greater infiltration cancer-associated fibroblasts at baseline. Clonotypic dynamics pre-existing intratumoral T cells hallmark responsive patients. These findings provide rational for anti-PD-L1 monotherapy as therapeutic strategy ClinicalTrials.gov identifier: NCT04215471 .

Язык: Английский

Процитировано

46
Tertiary lymphoid structures in anticancer immunity DOI
Jean‐Luc Teillaud, Ana Houel, Marylou Panouillot

и другие.

Nature reviews. Cancer, Год журнала: 2024, Номер 24(9), С. 629 - 646

Опубликована: Авг. 8, 2024

Язык: Английский

Процитировано

43