Accelerating and optimising CAR T-cell manufacture to deliver better patient products

The Lancet Haematology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

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Enhanced conversion of T cells into CAR T cells by modulation of the MAPK/ERK pathway

Cell Reports Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 101970 - 101970

Published: Feb. 1, 2025

Highlights•Bar-coded antibodies distinguish transduced and untransduced T cells by sc-multi-omics•Transduction-resistant upregulate interferon-stimulated genes•Differentially expressed genes are consistent between healthy donors patients•Inhibitors of the ERK signaling pathway increase transduction CAR cell generationSummaryDelivery chimeric antigen receptors (CARs) to is usually mediated lentiviral vectors (LVs), which can have broad tropism or be targeted. To better understand molecular events during generation, with four different LVs followed single-cell multi-omics analysis, distinguishing vector signal but no CAR. We find that only a fraction encounter convert into cells. Single-cell transcriptome data reveal upregulated in non-transduced cells, whereas extracellular signal-regulated kinase (ERK)2 phosphatases This expression pattern evident from patients. The role mitogen-activated protein (MAPK)/ERK generation confirmed chemical inhibitors. These provide insights implications for improving generation.Graphical abstract

Language: Английский

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CAR-T therapy in solid tumors

Cancer Cell, Journal Year: 2025, Volume and Issue: 43(4), P. 665 - 679

Published: April 1, 2025

Language: Английский

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Contemporary Approaches to Immunotherapy of Solid Tumors

Cancers, Journal Year: 2024, Volume and Issue: 16(12), P. 2270 - 2270

Published: June 19, 2024

In recent years, the arrival of immunotherapy industry has introduced possibility providing transformative, durable, and potentially curative outcomes for various forms malignancies. However, further research shown that there are a number issues significantly reduce effectiveness immunotherapy, especially in solid tumors. First all, these problems related to protective mechanisms tumor its microenvironment. Currently, major efforts focused on overcoming by using different adoptive cell therapy variants modifications genetically engineered constructs. addition, complex workforce is required develop implement treatments. To overcome significant challenges, innovative strategies approaches necessary engineer more powerful variations with improved antitumor activity decreased toxicity. this review, we discuss innovations aimed at improving clinical efficacy tumors, as well limitations immunotherapies.

Language: Английский

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Impacts of transient exposure of human T cells to low oxygen, temperature, pH and nutrient levels relevant to bioprocessing for cell therapy applications

Cytotherapy, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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High NK Cell Levels at the End of Obinutuzumab Treatment Are Associated with Negative Minimal Residual Disease (MRD) in Chronic Lymphocytic Leukemia (CLL)

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

NK-cell antibody-dependent cell-mediated cytotoxicity (ADCC) is one of the main mechanisms action anti-CD20 monoclonal antibodies, which may affect outcome patients with chronic lymphocytic leukemia (CLL). We assessed whether high post-treatment count in peripheral blood was associated increased negative minimal residual disease (MRD) receiving antibody-based therapy. Obinutuzumab forces interaction between NK cells and CLL cells, making number critical for efficacy this antibody. Normal cell counts after monotherapy are achieving MRD-negative status. Group A, who did not achieve status, had a mean 36.86 cells/µL, while B, achieved 202.29 cells/µL. MRD were measured three months completion treatment. The differences statistically significant (p < 0.05). These results underscore relevance evaluating as potential biomarker to predict success In conclusion, our study suggests that elevated treatment status patients.

Language: Английский

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Improving systemic delivery of oncolytic virus by cellular carriers

Cancer Biology and Medicine, Journal Year: 2025, Volume and Issue: 21(12), P. 1104 - 1119

Published: Jan. 17, 2025

Oncolytic virotherapy (OVT) is a promising option for cancer treatment. OVT involves selective oncolytic virus (OV) replication within cells, which triggers anti-tumor responses and immunostimulation. Despite potential, faces critical challenges, including insufficient tumor-specific targeting, results in limited tumor penetration variability therapeutic efficacy. These challenges are particularly pronounced solid tumors with complex microenvironments heterogeneous vascularization. A comprehensive research program currently underway to develop refine innovative delivery methods address these issues enhance precision principal area of investigation the utilization cellular carriers distribution OVs microenvironments, thereby optimizing immune system activation maximizing effects. This review offers overview current strategies that being used via goal improving clinical impact therapy.

Language: Английский

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Identification of the conditions and minimum requirements necessary for the release of autologous fresh CAR T-cell products under hospital exemption: a position paper from the WP-bioproduction of the UNITC consortium

Bone Marrow Transplantation, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 25, 2025

Language: Английский

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Advances in the Manufacturing of CAR-NK Cells for Cancer Immunotherapy

Methods in pharmacology and toxicology, Journal Year: 2025, Volume and Issue: unknown, P. 63 - 81

Published: Jan. 1, 2025

Language: Английский

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Establishing a scalable perfusion strategy for the manufacture of CAR‐T cells in stirred‐tank bioreactors using a quality‐by‐design approach

Bioengineering & Translational Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Abstract Chimeric antigen receptor T cell (CAR‐T) therapies show high remission rates for relapsed and refractory leukemia lymphoma. However, manufacturing challenges hinder their commercial viability patient accessibility. This study applied quality‐by‐design principles to identify perfusion critical process parameters CAR‐T expansion in stirred tank bioreactors maximize yields. A design of experiments the Ambr® 250 High Throughput Perfusion small‐scale bioreactor revealed that earlier starts (48 h vs. 96 post‐inoculation) higher (1.0 VVD 0.25 VVD) significantly increased cytotoxic yields without compromising quality attributes. Optimizing improved growth kinetics across donor samples, achieving densities >21 × 10 6 cells/mL 7 days, outperforming traditional fed‐batch static flask cultures. underscores importance optimizing highlights utility scale‐down models reducing time, costs risks associated with development.

Language: Английский

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