Based on a deterministic and stochastic process hybrid model, we use white noises to account for patient variabilities in treatment outcomes, use a hyperparameter to represent patient heterogeneity in a cohort, and construct a stochastic model in terms of Ito stochastic differential equations for testing the efficacy of three different treatment protocols in CAR T cell therapy. The stochastic model has three ergodic invariant measures which correspond to three unstable equilibrium solutions of the deterministic system, while the ergodic invariant measures are attractors under some conditions for tumor growth. As the stable dynamics of the stochastic system reflects long-term outcomes of the therapy, the transient dynamics provide chances of cure in short-term. Two stopping times, the time to cure and time to progress, allow us to conduct numerical simulations with three different protocols of CAR T cell treatment through the transient dynamics of the stochastic model. The probability distributions of the time to cure and time to progress present outcome details of different protocols, which are significant for current clinical study of CAR T cell therapy.
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http://dx.doi.org/10.1016/j.mbs.2024.109141 | DOI Listing |
J Nanobiotechnology
January 2025
Department of Laboratory, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710032, China.
Background: Cardiac fibrosis plays a critical role in the progression of various forms of heart disease, significantly increasing the risk of sudden cardiac death. However, currently, there are no therapeutic strategies available to prevent the onset of cardiac fibrosis.
Methods And Results: Here, biomimetic ATP-responsive nanozymes based on genetically engineered cell membranes are adapted to specifically recognize activated cardiac fibroblasts (CFs) for the treatment of cardiac fibrosis.
Nat Med
January 2025
Department of Hematology, University Hospital of Rennes, UMR U1236, INSERM, University of Rennes, French Blood Establishment, Rennes, France.
The risk of T cell malignancies after chimeric antigen receptor (CAR) T cell therapy is a concern, although the true incidence remains unclear. Here we analyzed the DESCAR-T registry database, encompassing all pediatric and adult patients with hematologic malignancies who received CAR T cell therapy in France since 1 July 2018. Of the 3,066 patients included (2,536 B cell lymphoma, 162 B cell acute lymphoblastic leukemia (ALL) and 368 multiple myeloma), 1,680 (54.
View Article and Find Full Text PDFNat Immunol
January 2025
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Chimeric antigen receptor T cells (CAR T cells) with T stem (T) cell-like phenotypic characteristics promote sustained antitumor effects. We performed an unbiased and automated high-throughput screen of a kinase-focused compound set to identify kinase inhibitors (KIs) that preserve human T cell-like CAR T cells. We identified three KIs, UNC10225387B, UNC10225263A and UNC10112761A, that combined in vitro increased the frequency of CD45RACCR7TCF1 T cell-like CAR T cells from both healthy donors and patients with cancer.
View Article and Find Full Text PDFTransplant Cell Ther
January 2025
Institute of Haematology, Royal Prince Alfred Hospital, SLHD, Sydney, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, NSW, Australia.
CD19 directed chimeric antigen receptor (CAR) T-cell therapy is now standard of care for relapsed/refractory large B-cell non-Hodgkin lymphoma. Despite good overall response rates, many patients still experience disease progression and therefore it is important to predict those at risk of relapse following CAR T-cell therapy. We performed a prospective study using a flow cytometric assay at a single treatment centre to assess early CAR T-cell expansion in vivo 6 - 9 days after CAR-T cell infusion.
View Article and Find Full Text PDFJ Adv Res
January 2025
Department of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China. Electronic address:
Background: Cancer immunotherapy has emerged as a groundbreaking approach in cancer treatment, primarily realized through the manipulation of immune cells, notably T cell adoption and immune checkpoint blockade. Nevertheless, the manipulation of T cells encounters formidable hurdles. Macrophages, serving as the pivotal link between innate and adaptive immunity, play crucial roles in phagocytosis, cytokine secretion, and antigen presentation.
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