A scalable, spin‐free approach to generate enhanced induced pluripotent stem cell–derived natural killer cells for cancer immunotherapy DOI Creative Commons
Gustavo Rodrigues Rossi,

Jane Sun,

Cheng‐Yu Lin

и другие.

Immunology and Cell Biology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 13, 2024

Abstract Natural killer (NK) cells play a vital role in innate immunity and show great promise cancer immunotherapy. Traditional sources of NK cells, such as the peripheral blood, are limited by availability donor variability. In addition, vitro expansion can lead to functional exhaustion gene editing challenges. This study aimed harness induced pluripotent stem cell (iPSC) technology provide consistent scalable source overcoming limitations traditional enhancing potential for immunotherapy applications. We developed human placental–derived iPSC lines using reprogramming techniques. Subsequently, an optimized two‐step differentiation protocol was introduced generate high‐purity cells. Initially, iPSCs were differentiated into hematopoietic‐like spin‐free embryoid bodies (EBs). EBs transferred ultra‐low attachment plates induce differentiation. iPSC‐derived (iNK) expressed common markers (NKp46, NKp30, NKp44, CD16 eomesodermin) at both RNA protein levels. iNK demonstrated significant resilience cryopreservation exhibited enhanced cytotoxicity. The incorporation chimeric antigen receptor (CAR) construct further augmented their cytotoxic potential. exemplifies feasibility generating with high purity capabilities, improved have cytotoxicity through CAR expression. Our findings offer promising pathway development cellular immunotherapies, highlighting critical challenges associated sources.

Язык: Английский

Exploring treatment options in cancer: Tumor treatment strategies DOI Creative Commons
Beilei Liu, Hongyu Zhou, Licheng Tan

и другие.

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

Опубликована: Июль 17, 2024

Traditional therapeutic approaches such as chemotherapy and radiation therapy have burdened cancer patients with onerous physical psychological challenges. Encouragingly, the landscape of tumor treatment has undergone a comprehensive remarkable transformation. Emerging fervently pursued modalities are small molecule targeted agents, antibody-drug conjugates (ADCs), cell-based therapies, gene therapy. These cutting-edge not only afford personalized precise targeting, but also provide enhanced comfort potential to impede disease progression. Nonetheless, it is acknowledged that these strategies still harbour untapped for further advancement. Gaining understanding merits limitations holds promise offering novel perspectives clinical practice foundational research endeavours. In this review, we discussed different modalities, including drugs, peptide antibody cell therapy, It will detailed explanation each method, addressing their status development, challenges, solutions. The aim assist clinicians researchers in gaining deeper diverse options, enabling them carry out effective advance more efficiently.

Язык: Английский

Процитировано

175

A new era of cancer immunotherapy: combining revolutionary technologies for enhanced CAR-M therapy DOI Creative Commons
Na Li,

Shinan Geng,

Zhenzhen Dong

и другие.

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Июнь 1, 2024

Abstract Significant advancements have been made in the application of chimeric antigen receptor (CAR)-T treatment for blood cancers during previous ten years. However, its effectiveness treating solid tumors is still lacking, necessitating exploration alternative immunotherapies that can overcome significant challenges faced by current CAR-T cells. CAR-based immunotherapy against shows promise with emergence macrophages, which possess robust phagocytic abilities, antigen-presenting functions, and ability to modify tumor microenvironment stimulate adaptive responses. This paper presents a thorough examination latest progress CAR-M therapy, covering both basic scientific studies clinical trials. study examines primary obstacles hindering realization complete potential as well strategies be employed these hurdles. With revolutionary technologies like situ genetic modification, synthetic biology techniques, biomaterial-supported gene transfer, provide wider array resources manipulating tumor-associated we suggest combining advanced methods will result creation new era therapy demonstrates improved efficacy, safety, availability. Graphical

Язык: Английский

Процитировано

20

Lineage-tracing hematopoietic stem cell origins in vivo to efficiently make human HLF+ HOXA+ hematopoietic progenitors from pluripotent stem cells DOI Creative Commons

Jonas L. Fowler,

Sherry Li Zheng,

Alana Nguyen

и другие.

Developmental Cell, Год журнала: 2024, Номер 59(9), С. 1110 - 1131.e22

Опубликована: Апрель 2, 2024

The developmental origin of blood-forming hematopoietic stem cells (HSCs) is a longstanding question. Here, our non-invasive genetic lineage tracing in mouse embryos pinpoints that artery endothelial generate HSCs. Arteries are transiently competent to HSCs for 2.5 days (∼E8.5–E11) but subsequently cease, delimiting narrow time frame HSC formation vivo. Guided by the arterial origins blood, we efficiently and rapidly differentiate human pluripotent (hPSCs) into posterior primitive streak, lateral mesoderm, endothelium, hemogenic >90% pure progenitors within 10 days. hPSC-derived T, B, NK, erythroid, myeloid vitro and, critically, express hallmark transcription factors HLF HOXA5-HOXA10, which were previously challenging upregulate. We differentiated hPSCs highly enriched HLF+ HOXA+ with near-stoichiometric efficiency blocking unwanted lineages at each differentiation step. could avail both basic research cellular therapies.

Язык: Английский

Процитировано

18

Challenges and Future Perspectives in Modeling Neurodegenerative Diseases Using Organ‐on‐a‐Chip Technology DOI Creative Commons
Francesca Michela Pramotton, Sarah Spitz,

Roger D. Kamm

и другие.

Advanced Science, Год журнала: 2024, Номер 11(32)

Опубликована: Июнь 23, 2024

Abstract Neurodegenerative diseases (NDDs) affect more than 50 million people worldwide, posing a significant global health challenge as well high socioeconomic burden. With aging constituting one of the main risk factors for some NDDs such Alzheimer's disease (AD) and Parkinson's (PD), this societal toll is expected to rise considering predicted increase in population limited progress development effective therapeutics. To address failure rates clinical trials, legislative changes permitting use alternatives traditional pre‐clinical vivo models are implemented. In regard, microphysiological systems (MPS) organ‐on‐a‐chip (OoC) platforms constitute promising tool, due their ability mimic complex human‐specific tissue niches vitro. This review summarizes current modeling using OoC technology discusses five critical aspects still insufficiently addressed date. Taking these into consideration future MPS will advance vitro translational value setting.

Язык: Английский

Процитировано

12

Targeted Light-Induced Immunomodulatory Strategy for Implant-Associated Infections via Reversing Biofilm-Mediated Immunosuppression DOI
Feng Jiang, Jian Wang, Zun Ren

и другие.

ACS Nano, Год журнала: 2024, Номер 18(9), С. 6990 - 7010

Опубликована: Фев. 22, 2024

The clinical treatment efficacy for implant-associated infections (IAIs), particularly those caused by Methicillin-resistant Staphylococcus aureus (MRSA), remains unsatisfactory, primarily due to the formation of biofilm barriers and resulting immunosuppressive microenvironment, leading chronicity recurrence IAIs. To address this challenge, we propose a light-induced immune enhancement strategy, synthesizing BSA@MnO2@Ce6@Van (BMCV). BMCV exhibits precise targeting adhesion S. biofilm-infected region, coupled with its capacity catalyze oxygen generation from H2O2 in hypoxic acidic microenvironment (BME), promoting oxygen-dependent photodynamic therapy while ensuring continuous release manganese ions. Notably, targeted can penetrate biofilms, producing ROS that degrade extracellular DNA, disrupting structure impairing barrier function, making it vulnerable infiltration elimination system. Furthermore, reactive species (ROS) around lyse aureus, triggering bacterium-like immunogenic cell death (ICD), releasing abundant costimulatory factors, facilitating recognition maturation antigen-presenting cells (APCs), activating adaptive immunity. Additionally, ions BME act as immunoadjuvants, further amplifying macrophage-mediated innate responses reversing immunologically cold an hot BME. We prove our synthesized elicits robust response vivo, effectively clearing primary IAIs inducing long-term memory prevent recurrence. Our study introduces potent immunomodulatory nanoplatform capable biofilm-induced biofilm-mediated protective barriers, offering promising immunotherapeutic strategy addressing challenging

Язык: Английский

Процитировано

9

Structure characterization and intestinal immune promotion effect of polysaccharide purified from Alhagi camelorum Fisch DOI

Zulikeyan Manafu,

Ronglijiao Du,

Tuerhong Kudereti

и другие.

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 269, С. 132077 - 132077

Опубликована: Май 8, 2024

Язык: Английский

Процитировано

9

Innate Immune Cells in Tumour Microenvironment: A New Frontier in Cancer Immunotherapy DOI Creative Commons
Changhui Li, Xinyu Yu, Xinyan Han

и другие.

iScience, Год журнала: 2024, Номер 27(9), С. 110750 - 110750

Опубликована: Авг. 17, 2024

Innate immune cells, crucial in resisting infections and initiating adaptive immunity, play diverse significant roles tumor development. These including macrophages, granulocytes, dendritic cells (DCs), innate lymphoid innate-like T are pivotal the microenvironment (TME). components of TME, based on which various immunotherapy strategies have been explored. Immunotherapy strategies, such as novel checkpoint inhibitors, STING/CD40 agonists, macrophage-based surface backpack anchoring,

Язык: Английский

Процитировано

9

Preclinical application of a CD155 targeting chimeric antigen receptor T cell therapy for digestive system cancers DOI
Kai Zhang,

Yang Mi,

Bohao Zhang

и другие.

Oncogene, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

1

Are monocytes a preferable option to develop myeloid cell-based therapies for solid tumors? DOI Creative Commons

Daisy Bhatia,

Riccardo Dolcetti, Roberta Mazzieri

и другие.

Journal of Experimental & Clinical Cancer Research, Год журнала: 2025, Номер 44(1)

Опубликована: Март 15, 2025

Abstract In the last two decades, novel and promising cell-based therapies have populated treatment landscape for haematological tumors. However, commonly exploited T NK show limited applicability to solid This is mainly given by impaired tumor trafficking capability effector activity of these cells within a highly immunosuppressive microenvironment. Myeloid spontaneously home tumors can thus be reprogrammed and/or engineered directly attack or locally selectively deliver therapeutically relevant payloads that may improve efficacy immunotherapy against difficult-to-access context myeloid therapies, adoptive transfer monocytes has often been overshadowed infusion differentiated macrophages hematopoietic stem cell transplantation despite their therapeutic potential. Here, we summarize recent improvements benefits using tumors, current clinical applications challenges use as well some possible strategies overcome them.

Язык: Английский

Процитировано

1

Engineered stem cell-based strategy: A new paradigm of next-generation stem cell product in regenerative medicine DOI
Han Han,

Bi‐Te Chen,

Liu Yang

и другие.

Journal of Controlled Release, Год журнала: 2023, Номер 365, С. 981 - 1003

Опубликована: Дек. 21, 2023

Язык: Английский

Процитировано

20