Basic Concepts and Indications of CAR T Cells

Hämostaseologie, Год журнала: 2025, Номер 45(01), С. 014 - 023

Опубликована: Фев. 1, 2025

Abstract Chimeric antigen receptor (CAR) T cell therapy has revolutionized cancer immunotherapy, particularly for hematological malignancies. This personalized approach is based on genetically engineering cells derived from the patient to target antigens expressed—among others—on malignant cells. Nowadays they offer new hope where conventional therapies, such as chemotherapy and radiation, have often failed. Since first FDA approval in 2017, CAR rapidly expanded, proving highly effective against previously refractory diseases with otherwise a dismal outcome. Despite its promise, continues face significant challenges, including complex manufacturing, management of toxicities, resistance mechanisms that impact long-term efficacy, limited access well high costs, which continue shape ongoing research clinical applications. review aims provide an overview therapy, fundamental concepts, applications, current future directions

Язык: Английский

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Severe hypophosphatemia following idecabtagene vicleucel regardless of the severity of cytokine release syndrome

Cytotherapy, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Oncolytic viruses expressing MATEs facilitate target-independent T-cell activation in tumors

EMBO Molecular Medicine, Год журнала: 2025, Номер unknown

Опубликована: Янв. 9, 2025

Abstract Oncolytic viruses (OV) expressing bispecific T-cell engagers (BiTEs) are promising tools for tumor immunotherapy but the range of target tumors is limited. To facilitate effective stimulation with broad-range applicability, we established membrane-associated (MATEs) harboring protein transduction domain HIV-Tat to achieve non-selective binding cells. In vitro, MATEs effectively activated murine T cells and improved killing MC38 colon carcinoma Similarly, humanized in PBMCs from human donors. MC38-tumors mice, MATE-expression by oncolytic adenovirus Ad5/11 facilitated intratumoral activation, reduced growth prolonged survival accompanied infiltration tumor-directed CD8 + CD8/CD4 ratio. Absence early activation draining lymph nodes suggests safe applicability this strategy. Furthermore, was capable breaking resistance αPD-1 checkpoint therapy thereby promoting T-cell/tumor cell proximity clustering CD4 summary, demonstrated that MATE OVs powerful activating suitable local a broad tumors.

Язык: Английский

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Chimeric Antigen Receptor-T Cells in the Modern Era of Chronic Lymphocytic Leukemia Treatment

Cancers, Год журнала: 2025, Номер 17(2), С. 268 - 268

Опубликована: Янв. 15, 2025

Pathway inhibitors targeting Bruton tyrosine kinase (BTK) and B-cell lymphoma-2 (BCL-2) have dramatically changed the treatment landscape for both treatment-naïve relapsed/refractory chronic lymphocytic leukemia (CLL). However, with increased utilization, a growing number of patients will experience progressive disease on agents. This subgroup “double refractory” has limited options poor prognosis. Chimeric antigen receptor (CAR)-T cells transformed malignancies. Although earliest success CAR-T cell therapy was in CLL, clinical application this modality lagged until recent approval first product CLL. In review, we describe current upfront subsequent therapies unmet need novel agents highlighted by burgeoning role challenges therapy.

Язык: Английский

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Critical Care Considerations of Chimeric Antigen Receptor (CAR) T-Cell Therapy

Respiratory Medicine, Год журнала: 2025, Номер unknown, С. 107958 - 107958

Опубликована: Янв. 1, 2025

Язык: Английский

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Targets Selection for Precision Therapy of Relapsed/Refractory Multiple Myeloma: the Latest Advancements

Current Treatment Options in Oncology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 31, 2025

Язык: Английский

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The road ahead for chimeric antigen receptor T cells

The Journal of Immunology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 10, 2025

Abstract Chimeric antigen receptor T (CART) cell therapy is an innovative form of immunotherapy that has shown remarkable and long-term responses in patients with B-cell malignancies. Over the years, field made significant progress our understanding successes challenges associated CART therapy. In this review, we provide overview current state clinic. We detail including patient access, CART-associated toxicity, tumor heterogeneity, trafficking, microenvironment, different fates. With each challenge, review lessons learned, potential solutions outline areas for future development. Finally, discuss how engineered moving into treatment solid tumors other diseases beyond cancer.

Язык: Английский

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Optimizing cancer treatment: the synergistic potential of CAR-T cell therapy and CRISPR/Cas9

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Ноя. 8, 2024

Optimizing cancer treatment has become a pivotal goal in modern oncology, with advancements immunotherapy and genetic engineering offering promising avenues. CAR-T cell therapy, revolutionary approach that harnesses the body's own immune cells to target destroy cells, shown remarkable success, particularly treating acute lymphoblastic leukemia (ALL), other hematologic malignancies. While therapy promise, challenges such as high cost manufacturing complexity remain. However, its efficacy solid tumors remains limited. The integration of CRISPR/Cas9 technology, powerful precise genome-editing tool, also raises safety concerns regarding unintended edits off-target effects, offers synergistic potential overcome these limitations. can enhance by improving specificity persistence reducing resistance tumor-induced immunosuppression. This combination facilitate knockout checkpoint inhibitors, boosting anti-tumor activity cells. Recent studies have demonstrated CRISPR/Cas9-edited previously untreatable types, new hope for patients refractory cancers. not only enhances but paves way personalized therapies tailored individual profiles. review highlights ongoing research efforts refine this explores revolutionize across broader range As progresses, holds promise transforming treatment, making it more effective accessible. current advancements, challenges, future prospects innovative therapeutic strategy.

Язык: Английский

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Immune safety challenges facing the preclinical assessment and clinical progression of cell therapies

Drug Discovery Today, Год журнала: 2024, Номер 29(12), С. 104239 - 104239

Опубликована: Ноя. 8, 2024

Язык: Английский

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Pharmacological Activation of SIRT3 Modulates the Response of Cancer Cells to Acidic pH

Pharmaceuticals, Год журнала: 2024, Номер 17(6), С. 810 - 810

Опубликована: Июнь 20, 2024

Cancer cells modulate their metabolism, creating an acidic microenvironment that, in turn, can favor tumor progression and chemotherapy resistance. Tumor adopt strategies to survive a drop extracellular pH (pHe). In the present manuscript, we investigated contribution of mitochondrial sirtuin 3 (SIRT3) adaptation survival cancer low pHe. SIRT3-overexpressing silenced breast MDA-MB-231 human embryonic kidney HEK293 were grown buffered unbuffered media at 7.4 6.8 for different times. mRNA expression SIRT3 CAVB, was measured by RT-PCR. Protein SIRT3, CAVB autophagy proteins estimated western blot. SIRT3-CAVB interaction determined immunoprecipitation proximity ligation assays (PLA). Induction studied blot TEM. overexpression increases both cell lines. Moreover, demonstrated that controls intracellular (pHi) through regulation carbonic anhydrase VB (CAVB). Interestingly, obtained similar results using MC2791, new activator. Our point possibility modulating decrease response resistance ameliorate effectiveness anticancer therapy.

Язык: Английский

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