CAR T therapy beyond cancer: the evolution of a living drug

Nature, Год журнала: 2023, Номер 619(7971), С. 707 - 715

Опубликована: Июль 26, 2023

Язык: Английский

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Harnessing the potential of hydrogels for advanced therapeutic applications: current achievements and future directions

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Июль 1, 2024

The applications of hydrogels have expanded significantly due to their versatile, highly tunable properties and breakthroughs in biomaterial technologies. In this review, we cover the major achievements potential therapeutic applications, focusing primarily on two areas: emerging cell-based therapies promising non-cell modalities. Within context cell therapy, discuss capacity overcome existing translational challenges faced by mainstream therapy paradigms, provide a detailed discussion advantages principal design considerations for boosting efficacy as well list specific examples different disease scenarios. We then explore drug delivery, physical intervention therapies, other areas (e.g., bioadhesives, artificial tissues, biosensors), emphasizing utility beyond mere delivery vehicles. Additionally, complement our latest progress clinical application outline future research directions, particularly terms integration with advanced biomanufacturing This review aims present comprehensive view critical insights into selection both tailored meet requirements diverse diseases situations.

Язык: Английский

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Vaccine-boosted CAR T crosstalk with host immunity to reject tumors with antigen heterogeneity

Cell, Год журнала: 2023, Номер 186(15), С. 3148 - 3165.e20

Опубликована: Июль 1, 2023

Chimeric antigen receptor (CAR) T cell therapy effectively treats human cancer, but the loss of recognized by CAR poses a major obstacle. We found that in vivo vaccine boosting cells triggers engagement endogenous immune system to circumvent antigen-negative tumor escape. Vaccine-boosted promoted dendritic (DC) recruitment tumors, increased uptake DCs, and elicited priming anti-tumor cells. This process was accompanied shifts metabolism toward oxidative phosphorylation (OXPHOS) critically dependent on CAR-T-derived IFN-γ. Antigen spreading (AS) induced vaccine-boosted enabled proportion complete responses even when initial 50% negative, heterogeneous control further enhanced genetic amplification IFN-γ expression. Thus, CAR-T-cell-derived plays critical role promoting AS, provides clinically translatable strategy drive such against solid tumors.

Язык: Английский

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Principles and therapeutic applications of adaptive immunity

Cell, Год журнала: 2024, Номер 187(9), С. 2052 - 2078

Опубликована: Апрель 1, 2024

Adaptive immunity provides protection against infectious and malignant diseases. These effects are mediated by lymphocytes that sense respond with targeted precision to perturbations induced pathogens tissue damage. Here, we review key principles underlying adaptive orchestrated distinct T cell B populations their extensions disease therapies. We discuss the intracellular intercellular processes shaping antigen specificity recognition in immune activation lymphocyte functions mediating effector memory responses. also describe how balance protective autoimmunity immunopathology, including during tolerance, response chronic stimulation, adaptation non-lymphoid tissues coordinating homeostasis. Finally, extracellular signals cell-intrinsic programs underpinning conclude summarizing advances vaccination engineering responses for therapeutic interventions. A deeper understanding of these holds promise uncovering new means improve human health.

Язык: Английский

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Programming CAR T Cell Tumor Recognition: Tuned Antigen Sensing and Logic Gating

Cancer Discovery, Год журнала: 2023, Номер 13(4), С. 829 - 843

Опубликована: Март 24, 2023

Abstract The success of chimeric antigen receptor (CAR) T cells targeting B-cell malignancies propelled the field synthetic immunology and raised hopes to treat solid tumors in a similar fashion. Antigen escape paucity tumor-restricted CAR targets are recognized challenges fulfilling this prospect. Recent advances cell engineering extend toolbox receptors available calibrate sensitivity combine create adapted tumor-sensing cells. Emerging strategies lower threshold for effective recognition, when needed, enable composite recognition hold great promise overcoming tumor heterogeneity curbing off-tumor toxicities. Significance: Improving clinical efficacy therapies will require that overcome heterogeneous low-abundance target expression while minimizing reactivity normal tissues. design logic gating poised beyond malignancies.

Язык: Английский

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Forks in the road for CAR T and CAR NK cell cancer therapies

Nature Immunology, Год журнала: 2023, Номер 24(12), С. 1994 - 2007

Опубликована: Ноя. 27, 2023

Язык: Английский

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CD8+ T cell-based cancer immunotherapy

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Апрель 29, 2024

Abstract The immune system in humans is a defense department against both exogenous and endogenous hazards, where CD8 + T cells play crucial role opposing pathological threats. Various immunotherapies based on have emerged recent decades, showing their promising results treating intractable diseases. However, the fight constantly changing evolving cancers, formation function of can be challenged by tumors that might train group accomplices to resist cell killing. As cancer therapy stepped into era immunotherapy, understanding physiological cells, studying machinery tumor escape, thereby formulating different therapeutic strategies become imperative missions for clinical translational researchers fulfill. After brief basics cell-based biology covered, this review delineates mechanisms escape discusses immunotherapy regimens with own advantages setbacks, embracing challenges perspectives near future.

Язык: Английский

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Advances in Engineered Macrophages: A New Frontier in Cancer Immunotherapy

Cell Death and Disease, Год журнала: 2024, Номер 15(4)

Опубликована: Апрель 1, 2024

Abstract Macrophages, as pivotal cells within the tumour microenvironment, significantly influence impact of and reactions to treatments for solid tumours. The rapid evolution bioengineering technology has revealed vast potential engineered macrophages in immunotherapy, disease diagnosis, tissue engineering. Given this landscape, goal harnessing innovating a novel strategy immunotherapy cannot be overstated. diverse strategies realm cancer encompassing macrophage drug delivery systems, chimeric antigen receptor therapy, synergistic treatment approaches involving bacterial outer membrane vesicles macrophages, are meticulously examined review. These methodologies designed enhance therapeutic efficacy against tumours, particularly those that drug-resistant metastatic. Collectively, these immunotherapies poised supplement refine current paradigms, thus heralding new frontier fight malignant

Язык: Английский

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A new era of cancer immunotherapy: combining revolutionary technologies for enhanced CAR-M therapy

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Июнь 1, 2024

Abstract Significant advancements have been made in the application of chimeric antigen receptor (CAR)-T treatment for blood cancers during previous ten years. However, its effectiveness treating solid tumors is still lacking, necessitating exploration alternative immunotherapies that can overcome significant challenges faced by current CAR-T cells. CAR-based immunotherapy against shows promise with emergence macrophages, which possess robust phagocytic abilities, antigen-presenting functions, and ability to modify tumor microenvironment stimulate adaptive responses. This paper presents a thorough examination latest progress CAR-M therapy, covering both basic scientific studies clinical trials. study examines primary obstacles hindering realization complete potential as well strategies be employed these hurdles. With revolutionary technologies like situ genetic modification, synthetic biology techniques, biomaterial-supported gene transfer, provide wider array resources manipulating tumor-associated we suggest combining advanced methods will result creation new era therapy demonstrates improved efficacy, safety, availability. Graphical

Язык: Английский

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The emerging era of cell engineering: Harnessing the modularity of cells to program complex biological function

Science, Год журнала: 2022, Номер 378(6622), С. 848 - 852

Опубликована: Ноя. 24, 2022

A new era of biological engineering is emerging in which living cells are used as building blocks to address therapeutic challenges. These efforts distinct from traditional molecular engineering-their focus not on optimizing individual genes and proteins therapeutics, but rather using components modules reprogram how make decisions communicate achieve higher-order physiological functions vivo. This cell-centric approach enabled by a growing tool kit that can synthetically control core cell-level functional outputs, such where the body cell should go, what other it interact with, messages transmit or receive. The power has been clinically validated development immune designed kill cancer. same for rewiring connectivity beginning be engineer therapies host diseases program self-organization tissues organs. By forcing conceptual distillation complex into finite set instructions operate at level, these also shed light fundamental hierarchical logic links function.

Язык: Английский

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