Efficient combination of radiotherapy and CAR-T – A systematic review

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 174, P. 116532 - 116532

Published: April 3, 2024

Chimeric antigen receptor T (CAR-T) cell therapy, a groundbreaking immunotherapy. However, it faces formidable challenges in treating solid tumors, grappling with issues like poor trafficking, limited penetration, and insufficient persistence within the tumor microenvironment (TME). CAR-T cells are engineered to express receptors that target specific cancer antigens, enhancing their ability recognize eliminate cells. This review paper explores intricate interplay between therapy radiotherapy (RT), investigating synergistic potential. Radiotherapy, standard treatment, involves using high doses of radiation damage cells, disrupting grow divide. We highlight RT modulates TME, augments presentation, promotes immune infiltration, bolstering cell-mediated eradication. Molecular insights shed light on RT-induced alterations stroma, recruitment promotion, induction immunogenic death. Noteworthy, strategies, such as combining hypofractionated myeloid-derived suppressor blockade, underscore innovative approaches enhance tumors. Bridging indications for hematological malignancies discussed, emphasizing scenarios where strategically enhances efficacy. The critically evaluates bridge compared traditional chemotherapy, highlighting timing dosage considerations crucial optimizing outcomes. In summary, provides valuable into molecular mechanisms activated by strategies improve fostering deeper understanding combined potential treatment.

Language: Английский

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Immunotherapy Innovations in the Fight against Osteosarcoma: Emerging Strategies and Promising Progress

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(2), P. 251 - 251

Published: Feb. 8, 2024

Immunosuppressive elements within the tumor microenvironment are primary drivers of tumorigenesis and malignant advancement. The presence, as well crosstalk between myeloid-derived suppressor cells (MDSCs), osteosarcoma-associated macrophages (OS-Ms), regulatory T (Tregs), endothelial (ECs) with osteosarcoma cause poor prognosis OS. In addition, consequent immunosuppressive factors favor loss treatment potential. Nanoparticles offer a means to dynamically locally manipulate immuno-nanoparticles, which present promising strategy for transforming OS-TME. Additionally, chimeric antigen receptor (CAR) technology is effective in combating This review summarizes essential mechanisms OS-TME current immune-associated strategies. last part highlights limitations existing therapies offers insights into future research directions.

Language: Английский

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Cell surface GRP78-directed CAR-T cells are effective at treating human pancreatic cancer in preclinical models

Translational Oncology, Journal Year: 2023, Volume and Issue: 39, P. 101803 - 101803

Published: Oct. 26, 2023

Pancreatic cancer is a highly lethal solid malignancy with limited treatment options. Chimeric antigen receptor T (CAR-T) cell therapy has been successfully applied to treat hematological malignancies, but faces many challenges in tumors. One major challenge the shortage of tumor-selective targets. Cell surface GRP78 (csGRP78) expressed on various cells including pancreatic cancer, not normal cells, providing potential target for CAR-T cancer. Here, we demonstrated that csGRP78-directed (GRP78-CAR-T) effectively killed human lines Bxpc-3-luc, Aspc-1-luc and MIA PaCa-2-luc, stem-like derived from PaCa-2-luc vitro by luciferase-based cytotoxicity assay. Importantly, showed GRP78-CAR-T efficiently homed infiltrated cell-derived xenografts significantly inhibited tumor growth vivo performing mouse xenograft experiments. Interestingly, found gemcitabine increased csGRP78 expression gemcitabine-resistant coapplication led robust cytotoxic effect these vitro. Taken together, our study demonstrates alone or combination chemotherapy, selectively csGRP78-expressing suppress growth.

Language: Английский

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Therapeutic avenues for γδ T cells in cancer

Journal for ImmunoTherapy of Cancer, Journal Year: 2023, Volume and Issue: 11(11), P. e007955 - e007955

Published: Nov. 1, 2023

γδ T cells are regarded as promising effector lymphocytes for next-generation cancer immunotherapies. In spite of being relatively rare in human peripheral blood, more abundant epithelial tissues where many tumors develop, and have been shown to actively participate anticancer immunity cytotoxic or “type 1” immune orchestrators. A major asset tackling advanced cancers is their independence from antigen presentation via the histocompatibility complex, which clearly sets them apart conventional αβ cells. Here we discuss main therapeutic strategies based on These include antibody-based bispecific engagers adoptive cell therapies, either focused Vδ1 + Vδ2 T-cell subsets, can be expanded selectively differentiated engineered maximize antitumor functions. We review preclinical data that supports each under development; summarize clinical trials pursued towards establishing cell-based treatments solid hematological malignancies.

Language: Английский

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Charting new paradigms for CAR-T cell therapy beyond current Achilles heels

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: May 1, 2024

Chimeric antigen receptor-T (CAR-T) cell therapy has made remarkable strides in treating hematological malignancies. However, the widespread adoption of CAR-T is hindered by several challenges. These include concerns about long-term and complex manufacturing process, as well efficacy factors such tumor escape, exhaustion, immunosuppressive microenvironment. Additionally, safety issues like risk secondary cancers post-treatment, on-target off-tumor toxicity, immune effector responses triggered cells are significant considerations. To address these obstacles, researchers have explored various strategies, including allogeneic universal development, infusion non-activated quiescent T within a 24-hour period, vivo induction cells. This review comprehensively examines clinical challenges outlines strategies to overcome them, aiming chart pathways beyond its current Achilles heels.

Language: Английский

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Comparison of seven CD19 CAR designs in engineering NK cells for enhancing anti‐tumour activity

Cell Proliferation, Journal Year: 2024, Volume and Issue: unknown

Published: June 3, 2024

Abstract Chimeric antigen receptor‐natural killer (CAR‐NK) cell therapy is emerging as a promising cancer treatment, with notable safety and source diversity benefits over CAR‐T cells. This study focused on optimizing CAR constructs for NK cells to maximize their therapeutic potential. We designed seven CD19 expressed them in using retroviral system, assessing tumour‐killing efficacy persistence. Results showed all enhanced prolonged survival tumour‐bearing mice. In particular, CAR1 (CD8 TMD‐CD3ζ SD)‐NK superior treating animals exhibited persistence when combined OX40 co‐stimulatory domain. Of note, CAR1‐NK were most effective at lower effector‐to‐target ratios, while CAR4 TMD‐OX40 CD‐ FcεRIγ SD) compromised expansion ability. Superior rates noted mice treated CAR1‐, CAR2 TMD‐ SD)‐, CAR3 CD3ζ SD)‐ CAR4‐NK those CAR5 (CD28 CAR6 TMD‐4‐1BB CD‐CD3ζ 1‐ITAM CAR7 cells, CAR5‐NK showing the weakest anti‐tumour activity. Increased expression of exhaustion markers, especially CAR7‐NK suggests that combining CAR‐NK immune checkpoint inhibitors might improve outcomes. These findings provide crucial insights developing products clinical applications.

Language: Английский

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All-Rounder Liposomes in Cancer Immunotherapy: Strategies and Design Applications of Engineered Liposomal Nanomaterials

BioChip Journal, Journal Year: 2024, Volume and Issue: 18(2), P. 211 - 232

Published: April 3, 2024

Language: Английский

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Improving chimeric antigen receptor T-cell therapies by using artificial intelligence and internet of things technologies: A narrative review

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 974, P. 176618 - 176618

Published: April 26, 2024

Language: Английский

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CRISPR/Cas9 screening: unraveling cancer immunotherapy’s ‘Rosetta Stone’

Trends in Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(8), P. 736 - 749

Published: May 18, 2024

Clustered regularly interspaced palindromic repeats (CRISPR)-based technology, a powerful toolset for the unbiased functional genomic screening of biological processes, has facilitated several scientific breakthroughs in biomedical field. Cancer immunotherapy advanced treatment numerous malignancies that previously had restricted options or unfavorable outcomes. In realm cancer immunotherapy, application CRISPR/CRISPR-associated protein 9 (Cas9)-based genetic perturbation enabled identification genes, biomarkers, and signaling pathways govern various immunoreactivities, as well development effective immunotherapeutic targets. this review, we summarize advances CRISPR/Cas9-based outline targets identified via CRISPR based on cancer-type classification.

Language: Английский

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Green synthesis and characterization of AgNPs, liposomal loaded AgNPs and ZnPcS4 photosensitizer for enhanced photodynamic therapy effects in MCF-7 breast cancer cells

Photodiagnosis and Photodynamic Therapy, Journal Year: 2024, Volume and Issue: 48, P. 104252 - 104252

Published: June 18, 2024

Breast cancer remains a formidable challenge in oncology despite significant advancements treatment modalities. Conventional therapies such as surgery, chemotherapy, radiation therapy, and hormonal therapy have been the mainstay managing breast for decades. However, subset of patient's experiences failure, leading to disease recurrence progression. Therefore, this study investigates therapeutic potential green-synthesized silver nanoparticles (AgNPs) using an African medicinal plant (Dicoma anomala methanol root extract) reducing agent combating cancer. AgNPs were synthesized bottom-up approach later modified with liposomes (Lip) loaded photosensitizer (PS) zinc phthalocyanine tetrasulfonate (Lip@ZnPcS

Language: Английский

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