EGFRVIII and EGFR targeted chimeric antigen receptor T cell therapy in glioblastoma

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Сен. 19, 2024

Glioblastoma is the most common primary brain tumor. Although there have been significant advances in surgical techniques, chemo and immunotherapies, radiation therapy, outcomes continue to be devastating for these patients with minimal improvements survival. Chimeric antigen receptor T cell therapy a revolutionary approach that new pillar treatment of cancer. CAR has produced remarkable results hematological malignancies; however, multiple limitations currently prevent it from being first-line especially solid tumors. Epidermal growth factor classically amplified glioblastoma, variant, EGFR variant III, expressed on making an exciting potential target therapy. preclinical potential, clinical data heterogeneous. In this review, we assess state field EGFR-targeted cells.

Язык: Английский

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CAR T-cell Design-dependent Remodeling of the Brain Tumor Immune Microenvironment Modulates Tumor-associated Macrophages and Anti-glioma Activity

Cancer Research Communications, Год журнала: 2023, Номер 3(12), С. 2430 - 2446

Опубликована: Ноя. 16, 2023

Abstract Understanding the intricate dynamics between adoptively transferred immune cells and brain tumor microenvironment (TIME) is crucial for development of effective T cell–based immunotherapies. In this study, we investigated influence TIME chimeric antigen receptor (CAR) design on anti-glioma activity B7-H3–specific CAR T-cells. Using an immunocompetent glioma model, evaluated a panel seven fully murine B7-H3 CARs with variations in transmembrane, costimulatory, activation domains. We then changes following T-cell therapy using high-dimensional flow cytometry single-cell RNA sequencing. Our results show that five out six single costimulatory domains demonstrated robust functionality vitro. However, these had significantly varied levels antitumor vivo. To enhance therapeutic effectiveness persistence, incorporated 41BB CD28 costimulation through transgenic expression 41BBL CD28-based This was associated improved efficacy vitro but did not result similar improvements Analysis revealed influenced composition TIME, recruitment distinct macrophage endogenous subsets successful responses. Indeed, complete depletion CSF1R inhibitor abrogated activity. sum, our study highlights critical role its modulation mediating adoptive immunotherapy high-grade glioma. Significance: immunotherapies hold great potential treating cancers; however, they are hindered by challenging environment dampens their effectiveness. influences makeup tumors, underscoring need to target specific components improve performance, highlighting significance models functional systems optimize therapy.

Язык: Английский

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Reprogramming endothelial cells to empower cancer immunotherapy

Trends in Molecular Medicine, Год журнала: 2023, Номер 30(2), С. 126 - 135

Опубликована: Ноя. 30, 2023

Язык: Английский

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Harnessing the Transcriptional Signatures of CAR-T-Cells and Leukemia/Lymphoma Using Single-Cell Sequencing Technologies

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(4), С. 2416 - 2416

Опубликована: Фев. 19, 2024

Chimeric antigen receptor (CAR)-T-cell therapy has greatly improved outcomes for patients with relapsed or refractory hematological malignancies. However, challenges such as treatment resistance, relapse, and severe toxicity still hinder its widespread clinical application. Traditional transcriptome analysis provided limited insights into the complex transcriptional landscape of both leukemia cells engineered CAR-T-cells, well their interactions within tumor microenvironment. advent single-cell sequencing techniques, a paradigm shift occurred, providing robust tools to unravel complexities these factors. These techniques enable an unbiased cellular heterogeneity molecular patterns. are invaluable precise design, guiding gene-based T-cell modification, optimizing manufacturing conditions. Consequently, this review utilizes modern clarify intricacies CAR-Ts. The aim manuscript is discuss potential mechanisms that contribute failures CAR-T immunotherapy. We examine biological characteristics CAR-Ts, govern responses, adverse events. By exploring aspects, we hope gain deeper understanding therapy, which will ultimately lead broader therapeutic applications.

Язык: Английский

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Advancements in chimeric antigen receptor-expressing T-cell therapy for glioblastoma multiforme: Literature review and future directions

Neuro-Oncology Advances, Год журнала: 2024, Номер 6(1)

Опубликована: Янв. 1, 2024

Glioblastoma multiforme (GBM) is an aggressive cancer that has been difficult to treat and often requires multimodal therapy consisting of surgery, radiotherapy, chemotherapy. Chimeric antigen receptor-expressing (CAR-T) cells have efficacious in treating hematological malignancies, resulting several FDA-approved therapies. CAR-T more recently studied for the treatment GBM, with some promising preclinical clinical results. The purpose this literature review highlight commonly targeted antigens, results trials, novel modifications, potential solutions challenges exist become widely implemented effective eradicating GBM.

Язык: Английский

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