Recent synthetic biology advancements have shown that cells can be engineered to respond to external stimuli such as chemical compounds and light, which significantly improves the specificity and controllability of CAR T therapy. However, the lack of both spatiotemporal and depth control is still the main issue in the clinic of CAR T treatment. At the same time, mechanogenetics, capable of penetrating deep tissues with high spatiotemporal precision, is rapidly evolving and advancing to reveal its potential for cancer immunotherapy. In the past few years, researchers have demonstrated the precise and remote control of engineered cells with mechanical perturbation originated from ultrasound, which may become a new solution to circumvent the limitations of CAR T therapy in the future. This review will discuss mechanobiology and the state-of art designs of controllable CAR T cells. A specific focus of this review will be on the mechanical control of CAR T therapy.
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http://dx.doi.org/10.1016/j.copbio.2020.06.008 | DOI Listing |
Biomaterials
December 2024
School of Engineering, Vanderbilt University, Nashville, TN, 37235, USA. Electronic address:
Multiple myeloma (MM), a cancer of bone marrow plasma cells, is the second-most common hematological malignancy. However, despite immunotherapies like chimeric antigen receptor (CAR)-T cells, relapse is nearly universal. The bone marrow (BM) microenvironment influences how MM cells survive, proliferate, and resist treatment.
View Article and Find Full Text PDFCardiooncology
December 2024
Department of Cardiovascular Medicine, Mayo Clinic, 200 1 St SW, Rochester, MN, 55905, USA.
Background: CD19 CAR T-cell therapy is a novel anti-cancer treatment that has produced remarkable responses in relapsed or refractory B-cell hematological malignancies. Cytokine Release Syndrome (CRS) is a dysregulated immune response that frequently occurs after CAR T-cell infusion. It can cause cardiac dysfunction and circulatory collapse negatively impacting outcomes and survival.
View Article and Find Full Text PDFCytotherapy
December 2024
Pediatric Hematology Oncology, Hospital Vall´de Hebrón, Barcelona, Spain.
Background: The management of relapsed acute lymphoblastic leukemia (ALL) after hematopoietic stem cell transplantation (HSCT) has evolved significantly. Initially, treatment options were limited to palliative care, salvage chemotherapy, and second HSCT. Currently, the focus has shifted to innovative immunotherapies, particularly CAR T-cell therapy.
View Article and Find Full Text PDFCurr Res Transl Med
December 2024
Thermo Fisher Scientific, 5781 Van Allen Way, Carlsbad CA 92008, USA. Electronic address:
The traditional method of CAR T cell production involves lengthy ex-vivo culture times which can result in the reduction of crucial naïve T cell subsets. Moreover, traditional CAR T cell therapy manufacturing processes can prolong time-to-patient, potentially delaying patient treatment, and contribute to disease progression. In this study, we describe an innovative and semi-automated 24-hour CAR T manufacturing process that yields a higher percentage of naïve/stem-cell like T cells which showed high cytotoxic activity and cytokine release in vitro.
View Article and Find Full Text PDFLeuk Lymphoma
December 2024
Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Despite increasing utilization of CAR T-cell therapy, data are lacking regarding long term follow up and risk of infectious complications after the early period following CAR T-cell infusion. In this study, we sought to compare epidemiology and risk factors for early (≤ 3 months) and late (3 months to 1 year) infections. Data were retrospectively collected at six time points: pre-CAR T, day of infusion, and at 3, 6, 9, and 12 months post CAR-T infusion for all consecutive adult patients treated at our institution.
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