Transplantation and Cellular Therapy, Год журнала: 2025, Номер unknown
Опубликована: Фев. 1, 2025
Язык: Английский
Cellular and Molecular Immunology, Год журнала: 2024, Номер 21(10), С. 1089 - 1108
Опубликована: Авг. 12, 2024
Abstract In the past decade, chimeric antigen receptor (CAR)-T cell therapy has emerged as a promising immunotherapeutic approach for combating cancers, demonstrating remarkable efficacy in relapsed/refractory hematological malignancies both pediatric and adult patients. CAR-natural killer (CAR-NK) complements CAR-T by offering several distinct advantages. CAR-NK cells do not require HLA compatibility exhibit low safety concerns. Moreover, are conducive to “off-the-shelf” therapeutics, providing significant logistic advantages over cells. Both have shown consistent results malignancies. However, their against solid tumors remains limited due various obstacles including tumor trafficking infiltration, well an immuno-suppressive microenvironment. this review, we discuss recent advances current challenges of immunotherapies, with specific focus on application tumors. We also analyze depth drawbacks compared highlight CAR optimization. Finally, explore future perspectives these adoptive highlighting increasing contribution cutting-edge biotechnological tools shaping next generation cellular immunotherapy.
Язык: Английский
Процитировано
28
Cells, Год журнала: 2024, Номер 13(2), С. 146 - 146
Опубликована: Янв. 12, 2024
This last decade, chimeric antigen receptor (CAR) T-cell therapy has become a real treatment option for patients with B-cell malignancies, while multiple efforts are being made to extend this other malignancies and broader patient populations. However, several limitations remain, including those associated the time-consuming highly personalized manufacturing of autologous CAR-Ts. Technologies establish "off-the-shelf" allogeneic CAR-Ts low alloreactivity currently developed, strong focus on gene-editing technologies. Although these technologies have many advantages, they also limitations, double-strand breaks in DNA safety risks as well lack modulation. As an alternative, non-gene-editing provide interesting approach support development future, possibilities fine-tuning gene expression easy development. Here, we will review different ways can be manufactured discuss which used. The biggest hurdles successful summarized, finally, overview current clinical evidence comparison its counterpart given.
Язык: Английский
Процитировано
18
The Lancet Haematology, Год журнала: 2024, Номер 11(6), С. e459 - e470
Опубликована: Май 8, 2024
Язык: Английский
Процитировано
18
Journal of Hematology & Oncology, Год журнала: 2025, Номер 18(1)
Опубликована: Янв. 13, 2025
The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, signaling molecules that interact promote growth therapeutic resistance. Elucidating the intricate interactions between cells TME crucial in understanding progression challenges. A critical process induced by epithelial-mesenchymal transition (EMT), wherein epithelial acquire mesenchymal traits, which enhance their motility invasiveness progression. By targeting various components TME, novel investigational strategies aim disrupt TME's contribution EMT, thereby improving efficacy, addressing resistance, offering a nuanced approach therapy. This review scrutinizes key players emphasizing avenues therapeutically components. Moreover, article discusses implications for resistance mechanisms highlights current toward modulation along with potential caveats.
Язык: Английский
Процитировано
10
Frontiers in Immunology, Год журнала: 2023, Номер 14
Опубликована: Дек. 22, 2023
Lymphodepletion (LD) or conditioning is an essential step in the application of currently used autologous and allogeneic chimeric antigen receptor T-cell (CAR-T) therapies as it maximizes engraftment, efficacy long-term survival CAR-T. Its main modes action are depletion modulation endogenous lymphocytes, microenvironment for improved CAR-T expansion persistence, reduction tumor load. However, most LD regimens provide a broad fairly unspecific suppression T-cells well other hematopoietic cells, which can also lead to severe side effects, particularly infections. We reviewed 1271 published studies (2011-2023) with regard current strategies approved anti-CD19 products large B cell lymphoma (LBCL). Fludarabine (Flu) cyclophosphamide (Cy) (alone combination) were commonly agents. A number different schemes combinations have been reported. In respective schemes, doses Flu Cy (range 75-120mg/m2 750-1.500mg/m2) wash out times 2-5 days) differed substantially. Furthermore, agents such bendamustine (benda), busulfan alemtuzumab (for CAR-T) described. This diversity creates challenge but opportunity investigate impact on cellular kinetics clinical outcomes Only 21 explicitly investigated more detail influence safety efficacy. As potentially both vivo activity toxicity CAR-T, detailed analysis will be needed before we able fully assess its subsets within product. The T2EVOLVE consortium propagates strategic investigation protocols development optimized regimens.
Язык: Английский
Процитировано
40
Cancer Cell International, Год журнала: 2023, Номер 23(1)
Опубликована: Авг. 21, 2023
Abstract Skin cancer is one of the most widespread cancers, with a significant global health effect. UV-induced DNA damage in skin cells triggers them to grow and proliferate out control, resulting development. Two common types include melanoma (MSC) non-melanoma (NMSC). Melanoma lethal form cancer, NMSC includes basal cell carcinoma (BCC), squamous (SCC), other forms. The incidence increasing part owing demographic shift toward an aging population, which more prone NMSC, imposing considerable financial strain on public services. introduction immunostimulatory approaches for eradication has led improvements treatment. Over last three decades, monoclonal antibodies have been used as powerful human therapeutics besides scientific tools, along development antibody production design procedures from chimeric humanized then fully than 6 approved by food drug administration (FDA) successful In this review, we will discuss epidemiology, immunology, therapeutic different
Язык: Английский
Процитировано
35
Cancer Discovery, Год журнала: 2023, Номер 14(1), С. 120 - 141
Опубликована: Окт. 31, 2023
Abstract Failure of adoptive T-cell therapies in patients with cancer is linked to limited expansion and persistence, even memory-prone 41BB-(BBz)–based chimeric antigen receptor (CAR) T cells. We show here that BBz-CAR stem/memory differentiation persistence can be enhanced through epigenetic manipulation the histone 3 lysine 9 trimethylation (H3K9me3) pathway. Inactivation H3K9 trimethyltransferase SUV39H1 enhances cell long-term protecting mice against tumor relapses rechallenges lung disseminated solid models up several months after CAR infusion. Single-cell transcriptomic (single-cell RNA sequencing) chromatin opening assay for transposase accessible chromatin) analyses tumor-infiltrating cells early reprogramming into self-renewing, stemlike populations decreased expression dysfunction genes all subpopulations. Therefore, methylation by optimizes functional cells, limiting relapses, providing protection rechallenges. Significance: Limited hinders therapeutic responses patients. targeting methyltransferase 41BB-based increasing stemness/memory differentiation. This opens a safe path enhancing tumors. See related article Jain et al., p. 142. featured Selected Articles from Issue, 5
Язык: Английский
Процитировано
31
Cancer Chemotherapy and Pharmacology, Год журнала: 2023, Номер 92(6), С. 439 - 453
Опубликована: Сен. 28, 2023
Язык: Английский
Процитировано
23
Frontiers in Immunology, Год журнала: 2024, Номер 15
Опубликована: Март 13, 2024
Immune Checkpoint Inhibitors (ICIs) therapy has advanced significantly in treating malignant tumors, though most 'cold' tumors show no response. This resistance mainly arises from the varied immune evasion mechanisms. Hence, understanding transformation to 'hot' is essential developing effective cancer treatments. Furthermore, tumor profiling critical, requiring a range of diagnostic techniques and biomarkers for evaluation. The success immunotherapy relies on T cells' ability recognize eliminate cells. In absence cell infiltration leads ineffectiveness ICI therapy. Addressing these challenges, especially impairment activation homing, crucial enhance therapy's efficacy. Concurrently, strategies convert into ones, including boosting adoptive therapies such as cell-recruiting bispecific antibodies Chimeric Antigen Receptor (CAR) cells, are under extensive exploration. Thus, identifying key factors that impact vital creating treatments targeting tumors.
Язык: Английский
Процитировано
14
Cells, Год журнала: 2024, Номер 13(1), С. 101 - 101
Опубликована: Янв. 4, 2024
Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of malignant and non-malignant disorders. CARs are synthetic transmembrane receptors expressed on genetically modified immune effector cells, including T natural killer (NK) or macrophages, which able to recognize specific surface antigens target cells eliminate them. CAR-modified mediate cytotoxic antitumor effects via numerous mechanisms, perforin granzyme pathway, Fas Ligand (FasL) cytokine secretion. High hopes associated with prospective use CAR-T strategy against solid cancers, especially ones resistant standard oncological therapies, such as pancreatic cancer (PC). Herein, we summarize current pre-clinical clinical studies evaluating potential tumor-associated (TAA), cell toxicities, their efficacy in PC.
Язык: Английский
Процитировано
13