Seminars in Immunology, Год журнала: 2023, Номер 70, С. 101843 - 101843
Опубликована: Сен. 28, 2023
Язык: Английский
npj Aging, Год журнала: 2024, Номер 10(1)
Опубликована: Фев. 6, 2024
Abstract The involvement of cellular senescence in the initiation and propagation diseases is clearly characterized, making elimination senescent cells essential to treat age-related diseases. development senolytic drugs demonstrated that targeting these limits deterioration patients’ condition, by inducing apoptosis. Nevertheless, first generations senolytics which has been developed displayed their activities through specific mechanisms several limitations during clinical development. However, rational eliminate remains evident, with necessity develop therapies a context tissues. evolutions field drug discovery open way new generation therapies, such as immunological approaches (CAR-T cells, Antibody-Drug Conjugated or vaccines), require preliminary steps research identify markers specifically expressed on demonstrating promising effects. Currently, preclinical strategies appears more challenging avoid strong side effects, but expected results are commensurate hopes for treatments. In this review, we highlight fact classical approach based repurposing display limited efficacy probably reached its term recent complex extension interest domain different fields allow extend possibility discover powerful therapies. future treatment linked cell therapy immunotherapy offer best patients.
Язык: Английский
Процитировано
29
Blood Cancer Journal, Год журнала: 2024, Номер 14(1)
Опубликована: Дек. 3, 2024
Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment paradigms for hematological malignancies. However, more than half of these patients cannot achieve sustainable tumor control, partially due to inadequate potency CAR-T cells in eradicating cells. T are crucial components anti-tumor immune response, and multiple intrinsic features significantly influence outcomes cell therapy. Herein, we review progressing research on characteristics that impact effectiveness cells, including exhaustion, memory subsets, senescence, regulatory T-cells, CD4+ CD8+ ratio, metabolism, repertoire. With comprehensive insight into biological processes underlying successful therapy, will further refine applications novel therapeutic modalities, enhance their efficacy safety patients.
Язык: Английский
Процитировано
5
Molecular Aspects of Medicine, Год журнала: 2024, Номер 100, С. 101318 - 101318
Опубликована: Сен. 10, 2024
Язык: Английский
Процитировано
2
Cell Reports Medicine, Год журнала: 2024, Номер 5(11), С. 101827 - 101827
Опубликована: Ноя. 1, 2024
NKG2D ligands (NKG2DLs) are broadly expressed in cancer. To target these, we describe an adaptor chimeric antigen receptor (CAR) termed NKG2D/Dap10-12. Herein, T cells engineered to co-express with a fusion protein that comprises Dap10 joined Dap12 endodomain. NKG2D/Dap10-12 elicit compelling efficacy, eradicating or controlling NKG2DL-expressing tumors several established xenograft models. Importantly, durable responses, long-term survival, and rejection of tumor re-challenge reproducibly achieved. Efficacy is markedly superior clinical stage CAR analog, comprising NKG2D-CD3ζ fusion. Structure-function analysis using extended panel demonstrates potency dependent on membrane proximity signaling units, high cell surface expression, structure, provision exogenous Dap10, inclusion one rather than three immune tyrosine activation motifs per unit. Potent therapeutic impact also underpinned by enhanced oxidative phosphorylation, reduced senescence, transcriptomic re-programming for increased ribosomal biogenesis.
Язык: Английский
Процитировано
2
Journal for ImmunoTherapy of Cancer, Год журнала: 2024, Номер 12(8), С. e008665 - e008665
Опубликована: Авг. 1, 2024
Antitumor effect of chimeric antigen receptor (CAR)-T cells against solid tumors is limited due to various factors, such as low infiltration rate, poor expansion capacity, and exhaustion T within the tumor. NR4A transcription factors have been shown play important roles in T-cell mice. However, precise contribution each NR4a factor human differentiation remains be clarified.
Язык: Английский
Процитировано
2
Deleted Journal, Год журнала: 2024, Номер 32(4), С. 200897 - 200897
Опубликована: Окт. 18, 2024
Adoptive cell transfer with chimeric antigen receptor (CAR)-expressing T cells can induce remarkable complete responses in cancer patients. Therapeutic success has been correlated central and stem cell-like memory subsets the infusion product, which are better able to drive efficient CAR
Язык: Английский
Процитировано
1
Journal for ImmunoTherapy of Cancer, Год журнала: 2024, Номер 12(12), С. e009462 - e009462
Опубликована: Дек. 1, 2024
The treatment landscape for lymphoma and multiple myeloma, which disproportionally affect older adults, has been transformed by the advent of T cell-mediated immunotherapies, including immune checkpoint inhibition, cell-engaging bispecific antibodies, chimeric antigen receptor (CAR) cell therapy, during last decade. These modalities re-enable patient’s own system to combat malignant cells offer potential sustained remissions cure various diseases. Age profoundly affects physiological function system. process biological aging is largely driven inflammatory signaling, reciprocally fueled aging-related alterations physiology metabolism. In compartment, contributes senescence exhaustion, increased abundance terminally differentiated cells, a corresponding attrition in naïve numbers, decrease breadth repertoire. Furthermore, signaling drives pathologies frailty individuals. Thus, there growing evidence modulating efficacy toxicity immunotherapies. Here, we review available from clinical studies focusing on relationship between hematologic malignancies age. We discuss features potentially impacting outcomes scenarios, strategies improve safety inhibitors, CAR-T therapy patients.
Язык: Английский
Процитировано
1
British Journal of Haematology, Год журнала: 2024, Номер unknown
Опубликована: Дек. 12, 2024
Summary Chimeric antigen receptor (CAR) T‐cell therapy has emerged as a transformative treatment for aggressive B‐cell lymphomas (ABCL), However, about half of patients relapse, most them early. This study investigates the detection CAR copies in circulating cell‐free DNA (cfDNA) potential predictive biomarker early relapse (<6 months) to improve patient management. In this research, we have consecutively selected 73 ABCL treated with anti‐CD19 T‐cells, analysing levels peripheral blood and other clinical variables. Our results indicate that no correlation is present between genomic cfDNA; moreover, higher ‐cfDNA on day +14 after infusion (0.44 vs. 0.07; p = 0.019) are associated improved 6‐month progression‐free survival rates (74.2% 26%. < 0.01), suggesting could be strong predictor short‐term outcomes. These findings underscore integrating analysis into routine practice enhance prognostic accuracy therapeutic strategies undergoing therapy.
Язык: Английский
Процитировано
0
Опубликована: Май 14, 2024
In this webinar, our panelists will discuss recent developments and challenges for adoptive cell therapies cancer treatment. Our speakers introduce the different therapeutic approaches (tumor-infiltrating lymphocytes-therapy, chimeric antigen receptor (CAR)-T, CAR-NK, CAR-macrophages). The presentations be followed by a panel discussion Q A session. webinar hosted [Nature Communications](https://www.nature.com/ncomms/) [Communications Medicine](https://www.nature.com/commsmed) editors. journals also invite you to consider related collection on [Immune engineering therapy](https://www.nature.com/collections/dahdifegah), welcoming future submissions.
Язык: Английский
Процитировано
0
Frontiers in Immunology, Год журнала: 2024, Номер 15
Опубликована: Авг. 29, 2024
Chimeric antigen receptor T cell (CAR-T) is a promising treatment for aggressive Non-Hodgkin lymphoma (NHL). The aim of the meta-analysis was to determine association between metabolic tumor volumes (MTV) derived on positron emission tomography before CAR-T infusion and survival patients with NHL.
Язык: Английский
Процитировано
0