Allogeneic CD33-directed CAR-NKT cells for the treatment of bone marrow-resident myeloid malignancies

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 1, 2025

Abstract Chimeric antigen receptor (CAR)-engineered T cell therapy holds promise for treating myeloid malignancies, but challenges remain in bone marrow (BM) infiltration and targeting BM-resident malignant cells. Current autologous CAR-T therapies also face manufacturing patient selection issues, underscoring the need off-the-shelf products. In this study, we characterize primary samples identify a unique therapeutic opportunity CAR-engineered invariant natural killer (CAR-NKT) Using stem gene engineering clinically guided culture method, generate allogeneic CD33-directed CAR-NKT cells with high yield, purity, robustness. preclinical mouse models, exhibit strong BM homing effectively target blast cells, including CD33-low/negative leukemia progenitor Furthermore, synergize hypomethylating agents, enhancing tumor-killing efficacy. These show minimal off-tumor toxicity, reduced graft-versus-host disease cytokine release syndrome risks, resistance to allorejection, highlighting their substantial potential malignancies.

Language: Английский

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Boosting CAR-T cell therapy through vaccine synergy

Trends in Pharmacological Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Chimeric antigen receptor (CAR)-T cell therapy has transformed the treatment landscape for hematological cancers. However, achieving comparable success in solid tumors remains challenging. Factors contributing to these limitations include scarcity of tumor-specific antigens (TSAs), insufficient CAR-T infiltration, and immunosuppressive tumor microenvironment (TME). Vaccine-based strategies are emerging as potential approaches address challenges, enhancing expansion, persistence, antitumor efficacy. In this review, we explore diverse vaccine modalities, including mRNA, peptide, viral vector, dendritic (DC)-based vaccines, their roles augmenting responses. Special focus is given recent clinical advancements combining mRNA-based vaccines with genitourinary addition, discuss crucial considerations optimizing dosing, scheduling, delivery maximize synergy, aiming refine combination strategy improve efficacy safety.

Language: Английский

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Frontiers in CAR-T cell therapy for autoimmune diseases

Trends in Pharmacological Sciences, Journal Year: 2024, Volume and Issue: 45(9), P. 839 - 857

Published: Aug. 14, 2024

Chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy has demonstrated significant success in treating cancers. The potential of CAR-T cells is now being explored the context autoimmune diseases. Recent clinical trials have shown sustained and profound elimination autoreactive B by cells, leading to promising disease control with minimal safety concerns. These encouraging results inspired further investigation into applications for a broader range diseases development advanced products improved efficacy safety. In this review, we discuss mechanisms which target conditions, summarize current preclinical models, highlight ongoing trials, including design, outcomes, challenges. Additionally, limitations future directions treatment

Language: Английский

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Frontiers in artificial intelligence‐directed light‐sheet microscopy for uncovering biological phenomena and multiorgan imaging

View, Journal Year: 2024, Volume and Issue: 5(5)

Published: Sept. 3, 2024

Light-sheet fluorescence microscopy (LSFM) introduces fast scanning of biological phenomena with deep photon penetration and minimal phototoxicity. This advancement represents a significant shift in 3-D imaging large-scale tissues 4-D (space + time) small live animals. The large data associated LSFM requires efficient acquisition analysis the use artificial intelligence (AI)/machine learning (ML) algorithms. To this end, AI/ML-directed is an emerging area for multi-organ tumor diagnostics. review will present development highlight various configurations designs multi-scale imaging. Optical clearance techniques be compared effective reduction light scattering optimal deep-tissue further depict diverse range research translational applications, from organisms to diagnosis. In addition, address reconstruction, including application convolutional neural networks (CNNs) generative adversarial (GANs). summary, advancements have enabled post-imaging reconstruction analyses, underscoring LSFM's contribution advancing fundamental research.

Language: Английский

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Advancements in adoptive CAR immune cell immunotherapy synergistically combined with multimodal approaches for tumor treatment

Bioactive Materials, Journal Year: 2024, Volume and Issue: 42, P. 379 - 403

Published: Sept. 10, 2024

Language: Английский

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iPSC Technology Revolutionizes CAR-T Cell Therapy for Cancer Treatment

Bioengineering, Journal Year: 2025, Volume and Issue: 12(1), P. 60 - 60

Published: Jan. 13, 2025

Chimeric Antigen Receptor (CAR)-engineered T (CAR-T) cell therapy represents a highly promising modality within the domain of cancer treatment. CAR-T has demonstrated notable efficacy in treatment hematological malignancies, solid tumors, and various infectious diseases. However, current is autologous, which presents challenges related to high costs, time-consuming manufacturing processes, necessity for careful patient selection. A potential resolution this restriction could be found by synergizing technology with induced pluripotent stem (iPSC) technology. iPSC inherent capability furnish an inexhaustible reservoir resources. Experimental evidence successful generation human cells using technology, showcasing yield, purity, robustness, tumor-killing efficacy. Importantly, enables production clinical-grade cells, significantly reducing costs time, facilitating their use as allogeneic therapies treat multiple patients simultaneously. In review, we aim elucidate essential facets therapy, delineate its utility, enumerate advantages drawbacks, offer in-depth evaluation novel pragmatic approach

Language: Английский

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Synthetic Biology‐Based Engineering Cells for Drug Delivery

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

Published: Jan. 16, 2025

ABSTRACT Although drug delivery technology has promoted the clinical translation of small molecule drugs, there is an urgent need for advanced systems to overcome complex physiological barriers and increasing development biological drugs. This review overviews emerging applications synthetic biology‐based engineered cells delivery. We first introduce biology strategies engineer discuss benefits in terms specificity, intelligence, controllability. Furthermore, we highlight cutting‐edge advancements at convergence nanotechnology Nanotechnology expands engineering design construction concepts biology, drives biotechnology‐driven nanomaterial synthesis. In future, may be developed more modular, standardized, intelligent, leading significant breakthroughs systems.

Language: Английский

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Generating allogeneic CAR-NKT cells for off-the-shelf cancer immunotherapy with genetically engineered HSP cells and feeder-free differentiation culture

Nature Protocols, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Language: Английский

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Pluripotent stem cell-based immunotherapy: advances in translational research, cell differentiation, and gene modifications

Life Medicine, Journal Year: 2025, Volume and Issue: 4(1)

Published: Jan. 18, 2025

Abstract Cell-based immunotherapy, recognized as living drugs, is revolutionizing clinical treatment to advanced cancer and shaping the landscape of biomedical research for complex diseases. The differentiation human pluripotent stem cells (PSCs) emerges a novel platform with potential generate an unlimited supply therapeutic immune cells, especially when coupled gene modification techniques. PSC-based immunotherapy expected meet vast demand drugs. Here, we examine recent preclinical advances in focusing on PSC strategies methods producing cells. We also discuss opportunities this field challenges cell quality safety stresses need further transparency unlock full immunotherapies.

Language: Английский

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Allogeneic chimeric antigen receptors (CARs) as an “off-the-shelf” therapy in multiple myeloma

Immunotherapy, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 12

Published: Feb. 17, 2025

The success of autologous chimeric antigen receptor (CAR)-T cells has changed the treatment landscape in relapsed and refractory multiple myeloma (MM) resulting potential movement CAR-T to frontline setting. However, one greatest weaknesses this therapy is its nature, which makes it time-consuming, labor intensive, dependent on patient's T cell fitness. development allogeneic CARs critical overcome these challenges provide patients with an off-the-shelf alternative that readily available. This review will investigate current future perspectives CAR research MM, exploring both pre-clinical active clinical trials. More specifically, focus advantages disadvantages various cellular candidates including CAR-T, CAR-NK, CAR-iNKT cells, among other more novel candidates.

Language: Английский

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