Gambogic Acid Based Coordination Polymer Reinforces High‐Intensity Focused Ultrasound Treatment of Gynecologic Malignancies DOI
Lin Zhang, Xu Chen,

Mingzhuang Li

et al.

Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

Abstract High‐intensity focused ultrasound (HIFU) is emerging as a promising non‐invasive treatment for solid tumors. Nevertheless, HIFU may also induce the upregulation of Heat Shock Protein 90 (HSP‐90), potentially resulting in resistance to HIFU. Besides, although it effective against situ tumors, challenges remain with tumor metastasis and recurrence. Herein, innovative design gambogic acid (GA) based coordination polymer—GAZn‐PEG nanoparticles (GAZn‐PEG NPs) are synthesized through GA zinc ions (Zn 2+ ), subsequently functionalized lipid bilayer incorporating polyethylene glycol (PEG), sensitizing cervical ovarian cancers. Briefly, under exposure, markedly suppresses expression HSP‐90, thereby increasing tumor's sensitivity therapy. Furthermore, Zn not only overcome issue GA's poor water solubility but synergistically stimulate immune responses conjunction GA. More intriguingly, has been discovered that GAZn‐PEG can effectively activate cyclic GMP‐AMP synthase‐stimulator interferon genes (cGAS‐STING) pathway, enhancing provoked by Specifically, NPs show remarkable increase dendritic cell activation stimulation cGAS‐STING crucial long‐term protection recurrence metastasis.

Language: Английский

The diversity of natural killer cell functional and phenotypic states in cancer DOI

Kumar Rishabh,

Sandro Matosevic

Cancer and Metastasis Reviews, Journal Year: 2025, Volume and Issue: 44(1)

Published: Jan. 24, 2025

Language: Английский

Citations

0
CAR-CIK vs. CAR-T: benchmarking novel cytokine-induced killer cells as solid tumor immunotherapy in ErbB2+ rhabdomyosarcoma DOI Creative Commons
Laura M. Moser, Catrin Heim, Sebastian E. Koschade

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 3, 2025

Introduction CAR-T cell therapy, though successful in hematologic malignancies, faces challenges solid tumors due to limitations of autologous T cells. Cytokine-induced killer (CIK) cells can be given safely across allogeneic barriers and constitute alternative effector generated from healthy donors. CIK are a heterogenous population predominantly with mixed natural (NK) phenotype combine non-MHC-restricted cytotoxicity potent anti-tumor capacity the adaptive immune system. Here, we characterize compare efficacy, phenotypic subpopulations modes action CAR-CIK conventional same-donor samples ErbB2+ rhabdomyosarcoma (RMS). Methods To benchmark against cells, were lentivirally transduced second generation CD28-CD3ζ CAR. Effector their dynamics upon target exposure phenotypically characterized by flow cytometry. Efficacy was assessed human RMS cancer lines primary patient vitro ex vivo using spheroid co-incubation assays. Modes comparing cytokine secretion profiles bead-based multiplexed cytometry liquid chromatography mass spectrometry whole proteomics. Finally, used an model mimicking minimal metastatic residual disease potency vs. assess organ infiltration. Results In assays demonstrated superior tumor samples. Long-term spheroids led expansion enrichment CD3+CD56+ TNK signature showed significantly increased molecules like interferon-γ, perforin granulysin, lower Th2 cytokines IL-2, IL-4 IL-10. Whole proteomics corresponding upregulation chemokine signaling NK-cytotoxicity pathways NSG mice xenografted RMS, single injection either CAR-effector strongly impeded development improved survival. Conclusion Our results demonstrate that at least equipotent Combined favorable safety profile applicability, these findings position as promising effectors for tumors.

Language: Английский

Citations

0
In Vitro Evaluation of Genetically Unmodified Ligand-Armed Allogeneic Natural Killer Cells to Treat EGFR-Positive Glioblastoma DOI Creative Commons
Hortense Courot,

Émilie Rigal,

N. Adib

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(4), P. 254 - 254

Published: Feb. 11, 2025

Glioblastomas (GBMs) are lethal brain tumors in which EGFR gene amplification or mutation is frequently detected and associated with poor prognosis. The standard of care maximal resection followed by chemotherapy radiation. Over the last twenty years, marginal improvements patient survival have been achieved mainly through surgical techniques more accurate use In this study, umbilical cord blood-derived expanded human allogeneic natural killer (eNK) cells were pre-complexed to an Fc-engineered anti-EGFR monoclonal antibody (Pin-EGFR) create Pin-EGFR-armed eNK cells. showed vitro persistence mAb anchoring. This arming process mediated specific, rapid potent NK cell-redirected cytotoxicity against GBM cell lines patient-derived models consistent pathophysiological conditions GBM. These results demonstrate potential be effective therapy vitro. product represents a promising strategy directly target residual tumor tissue remaining at beyond margins immediately following surgery improve care.

Language: Английский

Citations

0
Safety and Efficacy of Immune Cell Therapeutics Targeting Α-Pd-L1 in Lung Cancer DOI

A-Ram Lee,

Hee Young Kang,

Lee Yu Bin

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0
Feeder-cell-free system for ex vivo production of natural killer cells from cord blood hematopoietic stem and progenitor cells DOI Creative Commons

Marta Martin Corredera,

Juliette Paillet, Pierre Gaudeaux

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 20, 2025

Natural Killer (NK) cells hold significant promise as therapeutic agents in immuno-oncology due to their ability target and eliminate cancerous infected without causing graft-versus-host disease or cytokine release syndrome. However, the limited availability of robust, scalable methods for generating clinical-grade NK remains a limiting factor broader clinical application. Here we report development novel feeder-cell-free culture system optimized producing from cord blood-derived CD34+ hematopoietic stem progenitor (HSPCs). Our method eliminates need feeder while achieving high yields that exhibit unique marker expression cytotoxic functions. Cord blood HSPCs were cultured our established hDLL 4 generated large numbers human T lymphoid progenitors (ProTcells) 7 days. ProTcells further hDLL4-free, cell differentiation supplemented with cytokines. Following 7- 14-day culture, this produced highly pure populations (>90% CD3-CD56+). Flow mass cytometric analysis confirmed activating receptors, transcription factors (ID2, T-bet) molecules (perforin, granzyme A/B), all essential ProT-NK functionality. These are an immature state, indicated by absence maturation markers (CD16, KIRs). Functional assays demonstrated these capable degranulation cytokines production (TNFα) upon stimulation K562 showed cytotoxicity against superior Peripheral Blood (PB)-NK. In NSG-Tg(hIL-15) mice, colonize bone marrow, liver, spleen persist mature marrow at least 9 days post-injection. Compared D21, D14 was functional homing potential. vivo, anti-tumor assay uses subcutaneous model has potential cells. ex vivo process supports yields, reducing dependency on mitigating contamination risks. findings demonstrate feasibility large, isolated readily available sources offer efficient alternative PB-NK therapies.

Language: Английский

Citations

0
Bistable dynamics of TAN-NK cells in tumor growth and control of radiotherapy-induced neutropenia in lung cancer treatment DOI Creative Commons
Donggu Lee,

Sun‐Ju Oh,

Sean E. Lawler

et al.

Mathematical Biosciences & Engineering, Journal Year: 2025, Volume and Issue: 22(4), P. 744 - 809

Published: Jan. 1, 2025

Language: Английский

Citations

0
A chimeric antigen receptor tailored to integrate complementary activation signals potentiates the antitumor activity of NK cells DOI Creative Commons
Eunbi Yi, Eunbi Lee, Hyo Jin Park

et al.

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

Citations

0
Inflammasomes in lymphocytes as therapeutic targets DOI
Zarema Albakova

Translational Oncology, Journal Year: 2025, Volume and Issue: 54, P. 102342 - 102342

Published: March 6, 2025

Language: Английский

Citations

0
Entinostat, a histone deacetylase inhibitor, enhances CAR-NK cell anti-tumor activity by sustaining CAR expression DOI Creative Commons

Donghyeon Jo,

Shelby Kaczmarek,

Abrar Ul Haq Khan

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 7, 2025

Allogeneic natural killer (NK) cell therapy has demonstrated significant potential in cancer immunotherapy by harnessing NK cells to target malignancies. CD138-targeting chimeric antigen receptor (CAR)-engineered offer a promising therapeutic option for multiple myeloma (MM). However, sustaining CAR expression on CAR-NK during ex vivo expansion poses challenge developing effective immunotherapies. In this study, primary were isolated, cryopreserved, and modified express anti-CD138 CARs through retroviral transduction. Histone deacetylase inhibitors (HDACi), particularly entinostat (ENT), applied enhance stability cells. Our findings indicate that ENT treatment significantly improves maintains expression, thereby enhancing the cytotoxic activity of against CD138-positive ENT-treated exhibited prolonged persistence more tumor reduction an MM tumor-bearing mouse model, highlighting HDACi-treated This study provides first evidence HDAC can sustain promoter-dependent manner, potentially anti-tumor efficacy underscoring possible need further clinical evaluation.

Language: Английский

Citations

0
CDH17-targeting CAR-NK cells synergize with CD47 blockade for potent suppression of gastrointestinal cancers DOI Creative Commons

Liuhai Zheng,

Yingqiao Ding, Xiaolong Xu

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0