Titrating chimeric antigen receptors on CAR T cells enabled by a microfluidic-based dosage-controlled intracellular mRNA delivery platform DOI
Yu‐Hsi Chen,

Mahnoor Mirza,

Ruoyu Jiang

и другие.

Biomicrofluidics, Год журнала: 2024, Номер 18(6)

Опубликована: Дек. 1, 2024

Chimeric antigen receptor (CAR) T-cell therapy shows unprecedented efficacy for cancer treatment, particularly in treating patients with various blood cancers, most notably B-cell acute lymphoblastic leukemia. In recent years, CAR therapies have been investigated other hematologic malignancies and solid tumors. Despite the remarkable success of therapy, cytokine release syndrome (CRS) is an unexpected side effect that potentially life-threatening. Our aim to reduce pro-inflammatory associated CRS by controlling surface density on T cells. We show expression can be titrated primary cells using acoustic-electric microfluidic platform. The platform performs dosage-controlled delivery uniformly mixing shearing cells, delivering approximately same amount gene coding mRNA into each cell.

Язык: Английский

From ex vivo to in vivo chimeric antigen T cells manufacturing: new horizons for CAR T-cell based therapy DOI Creative Commons
Eleonora Pinto, Lisa A. Lione, Mirco Compagnone

и другие.

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Янв. 4, 2025

Abstract In the past decades, Chimeric Antigen Receptor (CAR)-T cell therapy has achieved remarkable success, leading to approval of six therapeutic products for haematological malignancies. Recently, potential this also been demonstrated in non-tumoral diseases. Currently, manufacturing process produce clinical-grade CAR-T cells is complex, time-consuming, and highly expensive. It involves multiple steps, including collection T from patients or healthy donors, vitro engineering expansion, finally reinfusion into patients. Therefore, despite impressive clinical outcomes, ex vivo makes out reach many cancer Direct could be a more rapid solution able circumvent both complexity costs associated with manufactured cells. This novel approach allows completely eliminate manipulation expansion while producing populations directly vivo. To date, several studies have feasibility reprogramming, by employing injectable viral- nanocarrier-based delivery platforms tumour animal models. Additionally, production might reduce incidence, at least severity, systemic toxicities frequently occurring produced cells, such as cytokine release syndrome immune effector cell-associated neurotoxicity syndrome. review, we highlight challenges current protocols review latest progresses emerging field therapy, comparing various so far investigated. Moreover, offer an overview advantages deriving reprogramming other types, Natural Killer macrophages, CAR constructs.

Язык: Английский

Процитировано

2

NKG2A genetic deletion promotes human primary NK cell anti-tumor responses better than an anti-NKG2A monoclonal antibody DOI Creative Commons
Ying Gong,

Wilfred T.V. Germeraad,

Xu‐Lin Zhang

и другие.

Molecular Therapy, Год журнала: 2024, Номер 32(8), С. 2711 - 2727

Опубликована: Июнь 27, 2024

Natural killer (NK) cells eliminate infected or cancer via their cytotoxic capacity. NKG2A is an inhibitory receptor on NK and often overexpress its ligand HLA-E to evade cell surveillance. Given the successes of immune checkpoint blockade in therapy, interesting novel target. However, anti-NKG2A antibodies have shown limited clinical response. In pursuit enhancing cell-mediated anti-tumor responses, we devised a Cas9-based strategy delete KLRC1, encoding NKG2A, human primary cells. Our approach involved electroporation KLRC1-targeting Cas9 ribonucleoprotein resulting effective ablation expression. Compared with antibody blockade,

Язык: Английский

Процитировано

7

Artificially Tagging Tumors with Nano-Aluminum Adjuvant-Tethered Antigen mRNA Recruits and Activates Antigen-Specific Cytotoxic T Cells for Enhanced Cancer Immunotherapy DOI Creative Commons
Lingxiao Zhang, Jie Bai,

Aining Shen

и другие.

Biomaterials, Год журнала: 2025, Номер 317, С. 123085 - 123085

Опубликована: Янв. 5, 2025

T cell therapy for solid tumors faces significant challenges due to the immune off-target attack caused by loss of tumor surface antigens and inactivation in acidic microenvironment (TME). Herein, we developed a bifunctional immunomodulator (MO@NAL) loading ovalbumin (OVA; model antigen) mRNA (mOVA) onto lysozyme-coated layered double hydroxide nano-aluminum adjuvant (NA). The NA's inherent alkalinity effectively neutralizes excess acid within TME suppresses regulatory cells, creating favorable enhance cytotoxic infiltration activation tumors. Particularly, once internalization MO@NAL efficiently tags with OVA through carried mOVA, providing targets recruiting directing antigen-specific cells destroy cells. In mice pre-vaccinated vaccine, intratumoral administration rapidly awakens OVA-specific memory, inhibiting progression colon melanoma at both early advanced stages. non-pre-vaccinated mice, combining therapeutic vaccine or adoptive transfusion similarly achieves robust suppression. These findings thus underscore potential as an effective safe enhancing responses timely intervention progression.

Язык: Английский

Процитировано

1

mRNA Technology in Modern Medicine: Review and Future Prospects DOI Creative Commons
Heslley Machado Silva

Deleted Journal, Год журнала: 2025, Номер 2, С. 1 - 1

Опубликована: Янв. 17, 2025

Messenger RNA (mRNA) technology has revolutionized modern medicine, particularly in developing vaccines and gene therapies. While its prominence soared during the COVID-19 pandemic, foundation was built on decades of meticulous research. This review explores historical evolution mRNA technology, stabilization delivery breakthroughs, applications combating infectious diseases, cancer, genetic disorders. The study utilized a systematic search peer-reviewed articles from leading databases such as PubMed Scopus, focusing advancements clinical applications. Future potential treating chronic enhancing immunotherapy, addressing public health emergencies is also discussed, emphasizing need for sustained research innovation to harness transformative capabilities fully.

Язык: Английский

Процитировано

1

NK cell based immunotherapy against oral squamous cell carcinoma DOI Creative Commons
Ying Zhang, Jianming Xie, Haoran Wu

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Авг. 13, 2024

Oral squamous cell carcinoma (OSCC), a major subtype of head and neck cancers, presents significant challenges due to its aggressive feature limited therapeutic efficacy conventional treatments. In response these challenges, Natural Killer (NK) cells, vital component the innate immune system, are being explored for their potential in OSCC inherent ability target eliminate cancer cells without prior sensitization. This review uniquely focuses on evolving role NK specifically OSCC, incorporating recent advancements CAR-NK engineering personalized therapy approaches that have not been comprehensively covered previous reviews. The mechanisms through which exert cytotoxic effects tumor include direct killing engagement natural receptors antibody-dependent cellular cytotoxicity (ADCC), making them promising agents immunotherapy. Additionally, article explores enhance antitumor activity, such as modification with chimeric antigen (CARs) specific antigens. Clinical implications cell-based therapies, including integrating treatments existing protocols therapy, examined. highlights promise therapies improving outcomes patients outlines future directions research this dynamic field oncological

Язык: Английский

Процитировано

3

Immunotherapeutic Potential of the Yellow Fever Virus Vaccine Strain 17D for Intratumoral Therapy in a Murine Model of Pancreatic Cancer DOI Creative Commons
Alina S. Nazarenko, Yulia K. Biryukova, Kirill N. Trachuk

и другие.

Vaccines, Год журнала: 2025, Номер 13(1), С. 40 - 40

Опубликована: Янв. 6, 2025

Objective: We evaluate the immunotherapeutic potential of yellow fever virus vaccine strain 17D (YFV 17D) for intratumoral therapy pancreatic cancer in mice. Methods: The cytopathic effect YFV on mouse syngeneic cancers cells were studied both vitro and vivo human vitro. Results: demonstrated a strong against Although did not exhibit lytic Pan02 vitro, single administration caused delay tumor growth an increase median survival by 30%. Multiple injections further improve growth; however, it notably extended survival. Furthermore, preliminary immunization with enhanced its oncotherapeutic effect. Conclusions: Intratumoral delayed murine model cancer. fact that affected much more strongly than appears promising. Hence, we anticipate efficacy YFV-17D-based oncolytic will also be higher carcinomas compared to tumor.

Язык: Английский

Процитировано

0

Applications of mRNA Delivery in Cancer Immunotherapy DOI Creative Commons
Xiaoyu Pan,

Yang-Wen-Qing Zhang,

Caixia Dai

и другие.

International Journal of Nanomedicine, Год журнала: 2025, Номер Volume 20, С. 3339 - 3361

Опубликована: Март 1, 2025

Cancer treatment is continually advancing, with immunotherapy gaining prominence as a standard modality that has markedly improved the management of various malignancies. Despite these advancements, efficacy remains variable, certain cancers exhibiting limited response and patient outcomes differing considerably. Thus, enhancing effectiveness imperative. A promising avenue mRNA delivery, employing carriers such liposomes, peptide nanoparticles, inorganic exosomes to introduce cargos encoding tumor antigens, immune-stimulatory, or immune-modulatory molecules into immune microenvironment (TIME). This method aims activate system target eradicate cells. In this review, we characteristics limitations summarize application mechanisms currently prevalent in mRNA-based treatment. Additionally, given significant clinical checkpoint inhibitors (ICIs) chimeric antigen receptor (CAR)-based cell therapies solid tumors (including melanoma, non-small-cell lung cancer, head neck squamous carcinoma, triple-negative breast gastric cancer) leukemia, which have become first-line treatments, highlight discuss recent progress combining delivery ICIs, CAR-T, CAR-NK, CAR-macrophage therapies. combination enhances targeting capabilities ICIs CAR-cell-based therapies, while also mitigating long-term off-target toxicities associated conventional methods. Finally, analyze current systems, nuclease-induced instability, immunogenicity risks, complex carrier production, knowledge gaps concerning dosing safety. Addressing challenges crucial for unlocking potential cancer immunotherapy. Overall, exploring enriches our comprehension holds promise developing personalized effective strategies, potentially responses patients extending their survival time.

Язык: Английский

Процитировано

0

Chimeric antigen receptor NK cells for breast cancer immunotherapy DOI

Nisha Wu,

Ning Yang, Shiqi Zhang

и другие.

Cancer Treatment Reviews, Год журнала: 2025, Номер 137, С. 102943 - 102943

Опубликована: Апрель 23, 2025

Язык: Английский

Процитировано

0

Patient‐derived xenograft models in pan‐cancer: From bench to clinic DOI Creative Commons
Jiatong Li,

Ao Gu,

Nannan Tang

и другие.

Deleted Journal, Год журнала: 2025, Номер unknown

Опубликована: Май 25, 2025

Abstract Patient‐derived xenograft (PDX) models provide a robust preclinical platform that preserves the genetic and phenotypic heterogeneity of patient tumors while mirroring their tumor characteristics, which retain malignant cells pathological structure, making them valuable for studying progression developing anticancer therapies. This review outlines establishment PDX applications in research by comparing attributes limitations with other experimental models. It explores use understanding mechanisms, resistance treatment strategies, including radiotherapy, chemotherapy, targeted therapy, immunotherapy, nanotherapy, cell antibody‐drug conjugates, combination therapy. Integration multi‐omics technologies is also discussed, along application co‐clinical clinical studies. Notably, this covers approximately 30 cancer types aims to guide future research.

Язык: Английский

Процитировано

0

L’ingénierie cellulaire au service de l’optimisation des CAR-T cells DOI

Angélique Galatioto,

Maxime Fredon, Jeanne Galaine

и другие.

Bulletin de l Académie Nationale de Médecine, Год журнала: 2024, Номер 208(8), С. 1019 - 1029

Опубликована: Авг. 1, 2024

Процитировано

0