CAR T cells secreting NGF-neutralizing scFv enhance efficacy in clear cell renal cell carcinoma by relieving immunosuppression through immunosympathectomy DOI Creative Commons
Peiwei Yang, Xi Chen,

Yu Fan

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2024, Volume and Issue: 12(12), P. e009910 - e009910

Published: Dec. 1, 2024

Background Chimeric antigen receptor (CAR) T cells have demonstrated remarkable breakthroughs in treating hematologic malignancies, yet their efficacy solid tumors is limited by the immunosuppressive microenvironment. Sympathetic nerves significantly contribute to this milieu tumors. However, impact of tumor sympathetic denervation on enhancing CAR T-cell antitumor remains unclear. Methods We screened for gene sets various types cancers and investigated association with immunosuppression renal clear cell carcinoma. Using antibodies block nerve growth factor (NGF) pathway, we explored distribution tissues progression. Additionally, engineered secrete NGF single chain fragment variable (scFv) achieve immunosympathectomy assessed efficacy. Bulk RNA sequencing single-cell analyses were conducted evaluate changes immune phenotypes within Results Blocking pathway effectively reduced delayed scFv achieved a similar exhibited enhanced suppression. revealed that augmented effect was primarily due inhibition terminal exhaustion phenotype tumor-infiltrating CD8 prevention macrophage polarization from M1 M2. This approach maintained stronger state at site. splenic also more potent effector following infusion scFv-secreting cells. Conclusions Our results suggest novel weaken microenvironment synergistically enhance against

Language: Английский

A mathematical model to the melanoma dynamics involving CAR T-cells DOI
Gilberto César Lopes Rodrigues, Jairo G. Silva, Mostafa Adimy

et al.

Computational and Applied Mathematics, Journal Year: 2025, Volume and Issue: 44(1)

Published: Jan. 3, 2025

Language: Английский

Citations

0
Chimeric Antigen Receptor Cell Therapy: Empowering Treatment Strategies for Solid Tumors DOI Creative Commons
Tang‐Her Jaing, Yi-Wen Hsiao, Yi-Lun Wang

et al.

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(2), P. 90 - 90

Published: Jan. 31, 2025

Chimeric antigen receptor-T (CAR-T) cell therapy has demonstrated impressive efficacy in the treatment of blood cancers; however, its effectiveness against solid tumors been significantly limited. The differences arise from a range difficulties linked to tumors, including an unfriendly tumor microenvironment, variability within and barriers CAR-T infiltration longevity at location. Research shows that reasons for decreased cells treating are not well understood, highlighting ongoing need strategies address these challenges. Current frequently incorporate combinatorial therapies designed boost functionality enhance their capacity effectively target tumors. However, remain testing phase necessitate additional validation assess potential benefits. CAR-NK (natural killer), CAR-iNKT (invariant natural killer T), CAR-M (macrophage) emerging as promising Recent studies highlight construction optimization cells, emphasizing overcome unique challenges posed by such hypoxia metabolic barriers. This review focuses on CAR

Language: Английский

Citations

0
Challenges and overcoming strategies in CAR-T cell therapy for pediatric neuroblastoma DOI Creative Commons

Pei-Ting Ying,

Yongmin Tang

World Journal of Pediatrics, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

Language: Английский

Citations

0
Mathematical Model of CAR T-Cell Therapy for a B-Cell Lymphoma Lymph Node DOI Creative Commons
Soukaina Sabir, Odelaisy León-Triana, Sergio Serrano

et al.

Bulletin of Mathematical Biology, Journal Year: 2025, Volume and Issue: 87(3)

Published: Feb. 7, 2025

Abstract CAR T-cell therapies have demonstrated significant success in treating B-cell leukemia children and young adults. However, their effectiveness lymphomas has been limited comparison to leukemia. In this paper we present a mathematical model that elucidates the dynamics of diffuse large lymphoma T-cells lymph node. The aids understanding complex interplay between cell populations involved proposes ways identify potential underlying dynamical causes treatment failure. We also study phenomenon immunosuppression induced by tumor cells theoretically demonstrate its impact on dynamics. Through examination various response scenarios, underscore significance product characteristics outcomes.

Language: Английский

Citations

0
The clinical landscape of CAR NK cells DOI Creative Commons

Lasse Vedel Jørgensen,

Emil Birch Christensen,

Mike Bogetofte Barnkob

et al.

Experimental Hematology and Oncology, Journal Year: 2025, Volume and Issue: 14(1)

Published: March 27, 2025

Abstract Chimeric antigen receptor (CAR) NK cell therapy has emerged as a promising alternative to CAR T therapy, offering significant advantages in terms of safety and versatility. Here we explore the current clinical landscape cells, their application hematologic malignancies solid cancers, well potential for treating autoimmune disorders. Our analysis draws from data collected 120 trials focused on presents insights into demographics characteristics these studies. We further outline specific targets diseases under investigation, along with major sources, genetic modifications, combination strategies, preconditioning- dosing regimens, manufacturing strategies being utilized. Initial results 16 demonstrate efficacy particularly B malignancies, where response rates are comparable those seen cells but lower severe adverse effects, such cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity (ICANS), graft-versus-host disease (GvHD). However, challenges remain tumor applications, only modest been observed date. reveals that research is increasingly enhancing persistence, broadening therapeutic targets, refining processes improve accessibility scalability. With recent advancements engineering increased predicted become an integral component next-generation immunotherapies, not cancer potentially immune-mediated well.

Language: Английский

Citations

0
Mechanistic insights into resistance mechanisms to T cell engagers DOI Creative Commons
Liping Cao,

Gabrielle Leclercq-Cohen,

Christian Klein

et al.

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

Published: April 22, 2025

T cell engagers (TCEs) represent a groundbreaking advancement in the treatment of B and plasma malignancies are emerging as promising therapeutic approach for solid tumors. These molecules harness cells to bind eliminate cancer cells, effectively bypassing need antigen-specific recognition. Despite their established clinical efficacy, subset patients is either refractory TCE (e.g. primary resistance) or develops resistance during course therapy acquired treatment-induced resistance). In this review we comprehensively describe mechanisms TCEs, occurring both preclinical models trials with particular emphasis on cellular molecular pathways underlying process. We classify these into tumor intrinsic extrinsic ones. Tumor encompass changes within that impact cell-mediated cytotoxicity, including antigen loss, expression immune checkpoint inhibitory ligands intracellular render resistant killing. involve factors external presence an immunosuppressive microenvironment (TME) reduced functionality. further propose actionable strategies overcome offering potential avenues enhancing efficacy clinic.

Language: Английский

Citations

0
The Tumor Immune Environment: Advances in the Cancer Immunotherapy Era DOI
Adit Ben‐Baruch

Methods in molecular biology, Journal Year: 2025, Volume and Issue: unknown, P. 15 - 34

Published: Jan. 1, 2025

Language: Английский

Citations

0
The road after cancer: biomaterials and tissue engineering approaches to mediate the tumor microenvironment post-cancer treatment DOI Creative Commons
Lorna Westwood, Iain J. Nixon, Elaine Emmerson

et al.

Frontiers in Biomaterials Science, Journal Year: 2024, Volume and Issue: 3

Published: March 27, 2024

Cancer affects tens of millions the world’s population each year with a stark mortality rate. It is well established that in order to be effective treating solid tumor cancers, current treatment methods used often sacrifice surrounding healthy tissue and cause damage at site treatment, inducing changes microenvironment. These microenvironment can lead adverse side effects as long-term which continues have detrimental impact on patient’s quality life, even after remission. believed by modulating (TME) post-treatment, not only may efficacy treatments improved, but such associated negative effects, further complications arising from including metastasis, potential reduced. Mediating also considered aid repairing damaged subsequently making conditions more favourable for promoting regenerative processes. This review provides brief overview alterations TME resulting three main cancer treatments–chemotherapy, radiation therapy surgery–and most common engineering currently an attempt mediate post-cancer therapy. Furthermore, it investigates new emerging technologies within this field progress terms reaching clinical setting.

Language: Английский

Citations

3
Insight into the Progress in CAR-T Cell Therapy and Combination with Other Therapies for Glioblastoma DOI Creative Commons
Tingyu Liang, Yixuan Song,

Lingui Gu

et al.

International Journal of General Medicine, Journal Year: 2023, Volume and Issue: Volume 16, P. 4121 - 4141

Published: Sept. 1, 2023

Abstract: Glioblastoma (GBM) is the most common malignant primary brain cancer in adults. It always resistant to existing treatments, including surgical resection, postoperative radiotherapy, and chemotherapy, which leads a dismal prognosis high relapse rate. Therefore, novel curative therapies are urgently needed for GBM. Chimeric antigen receptor T (CAR-T) cell therapy has significantly improved life expectancy hematological malignancies patients, thus it increases interest applying CAR-T solid tumors. In recently published research, indicated that there numerous obstacles achieve clinical benefits tumors, especially GBM, because of GBM anatomical characteristics (the blood–brain barrier suppressive tumor microenvironment) heterogeneity. cells difficult penetrate barrier, immunosuppressive microenvironment (TME), induces exhaustion, impairs response. Moreover, under pressure therapy, heterogeneity plasticity drive evolution resistance, such as escape. Nonetheless, scientists strive strategies overcome these hurdles, designs regional delivery. For instance, structure multi-antigen-targeted can enrich accumulation TME eliminate abundant avoid Additionally, paired with an immune modifier one or more stimulating domains, different generation innovations manufacturing have efficacy persistence. While single receives limited survival benefit. Compared combination supplemented treatment paradigm. Combinatorial methods consolidate by regulating microenvironment, optimizing CAR structure, targeting cells, reversing tumor-immune escape mechanisms, represent promising avenue against based on multiple impressive research. exciting results also reported be realized through combining effective preclinical trials samples, aroused inspiration explore antitumor function therapies. summary, this study aims summarize limitation introduces enhance well prospect potential therapeutic combination. Keywords: CAR-T, strategies,

Language: Английский

Citations

7
Precision Targeting and Genetically Modified T Cells for Targeting Cancer Cells DOI Creative Commons

Dr Ammar A. Razzak Mahmood,

Sudhakar Srinivasan,

Challaraj Emmanuel E. S

et al.

International Journal of Trends in OncoScience, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 9

Published: Jan. 5, 2024

In this review cancer treatment, despite notable progress, challenges persist globally. Traditional methods like surgery, chemotherapy, and radiotherapy, while effective, often compromise patients' overall quality of life due to side effects. Immunotherapeutic strategies, especially Chimeric Antigen Receptor T cells, show promise by leveraging the immune system target tumors independently certain escape mechanisms. However, CAR-T cells' specificity surface antigens limits their applicability. Precise management demands ongoing research refine broaden these therapies. Employing CAR or T-cell receptor therapies, genetic engineering enhances antigenic specificity, optimizing immunotherapy precision. CARs, synthetic receptors engineered for tumor antigen recognition, represent a groundbreaking approach, intertwining immunotherapy, gene therapy, therapy. The human system's ability discern self from non-self-entities forms basis fostering innovative modalities that selectively cells. with FDA approval leukemia lymphoma, holds transformative potential but faces safety efficacy challenges. Advances, including mitigating cytotoxicity enhancing therapeutic efficacy, promise. Utilizing alteration, CARs have shown in treatment hematologic malignancies, particularly CD19 B cell blood cancers. Current study is investigating uses patients lymphoma myeloma.

Language: Английский

Citations

2