6 results on '"*ANTIGEN receptors"'
Search Results
2. CHARACTERIZATION OF HUMAN T CELLS AND NK CELLS EXPANDED WITH HUMAN PLATELET LYSATE FOR CHIMERIC ANTIGEN RECEPTOR BASED THERAPIES.
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Alonso-Camino, V. and Mirsch, B.
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T cells , *KILLER cells , *CHIMERIC antigen receptors , *BLOOD platelets , *CELL suspensions , *EMERGING infectious diseases , *T cell receptors , *MANUFACTURING cells - Abstract
T cells and NK cells expressing chimeric antigen receptors (CAR) have demonstrated potent clinical efficacy in patients with hematological malignancies. One of the issues to overcome in the treatment of solid tumors using CARs is the lack of a process that generates large amounts of CAR-T cells, reduces cell exhaustion and differentiation, and improves long term survival after infusion into patients. Previously, Torres Chavez et al. demonstrated in a series of in vitro and in vivo experiments, performed in both hematologic and solid tumor models, the profound qualitative impact on CAR-T cell performance after using human platelet lysate (hPL) as a cell growth supplement. T cells expanded with their hPL showed a good proliferative capacity and enhanced long-term in vivo persistence compared to Fetal Bovine Serum (FBS) or human AB Serum (ABS), resulting in superior anti-tumor effects. Additionally, this group demonstrated that the transduction of T cells to generate the CAR-T cells was significantly improved by the use of hPL. Mill Creek's human platelet lysate (hPL) is produced using expired human platelets obtained from accredited blood banks in the United States. These platelets were originally intended for use in patient transfusion. The safety of platelets used in transfusion is managed by the U.S. Food & Drug Administration (FDA), as well as the Association for the Advancement of Blood & Biotherapies (AABB). These organizations set standards, including testing for transmissible diseases. The United States record for blood safety is well established, with extremely low rates of disease transmission, making the platelet units used for hPL manufacture low risk. The Covid-19 pandemic has increased awareness of emerging infectious diseases, even though transmission of Covid-19 via blood transfusion has not been documented. For that reason, we developed gamma irradiated version of our products, which offer an additional safety measure in the clinic. Previously, we have shown that the use of our platelet lysates has the potential of significantly impacting T cell manufacture by improving the quality and potency of the end product. In this study, we compare the phenotypic profile of different subsets of peripheral blood lymphocytes cultured using our different hPL products versus serum derived products. Additionally we establish a protocol for large scale suspension culture, which could be used for expansion of allogeneic CAR cells. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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3. Adverse Cardiovascular and Pulmonary Events Associated With Chimeric Antigen Receptor T-Cell Therapy.
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Goldman, Adam, Maor, Elad, Bomze, David, Liu, Jennifer E., Herrmann, Joerg, Fein, Joshua, Steingart, Richard M., Mahmood, Syed S., Schaffer, Wendy L., Perales, Miguel-Angel, and Shouval, Roni
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CHIMERIC antigen receptors , *CARDIOVASCULAR diseases , *T cells , *CARDIOMYOPATHIES , *TACHYARRHYTHMIAS , *CYTOKINE release syndrome , *VENTRICULAR arrhythmia , *LUNG disease diagnosis , *CARDIOVASCULAR disease prevention , *LUNG disease prevention , *CARDIOVASCULAR disease diagnosis , *CARDIOTOXICITY , *BIOLOGICAL products , *IMMUNIZATION , *LUNG diseases , *PHARMACOLOGY , *CELL receptors , *DRUG monitoring , *RESEARCH funding , *DRUG side effects - Abstract
Background: Pivotal trials of chimeric antigen receptor T-cell (CAR-T) have identified common toxicities but may have been underpowered to detect cardiovascular and pulmonary adverse events (CPAEs).Objectives: This study sought to investigate CPAEs associated with commercial CD19-directed CAR-T therapy.Methods: In this retrospective, pharmacovigilance study, the authors used the Food and Drug Administration adverse event reporting system to identify CPAEs associated with axicabtagene-ciloleucel and tisagenlecleucel. The authors evaluated disproportionate reporting by the reporting odds ratio (ROR) and the lower bound of the information component 95% credibility interval (IC025 >0 is deemed significant). Significant associations were further adjusted to age and sex (adj.ROR).Results: The authors identified CAR-T reports of 2,657 patients, including 546 CPAEs (20.5%). CPAEs overlapped with cytokine release syndrome in 68.3% (373 of 546) of the reports. Compared with the full database, CAR-T was associated with overreporting of tachyarrhythmias (n = 74 [2.8%], adj.ROR = 2.78 [95% CI: 2.21-3.51]), cardiomyopathy (n = 69 [2.6%], adj.ROR = 3.51 [2.42-5.09]), pleural disorders (n = 46 [1.7%], adj.ROR = 3.91 [2.92-5.23]), and pericardial diseases (n = 11 [0.4%], adj.ROR = 2.26 [1.25-4.09], all IC025 >0). Venous thromboembolic events (VTEs) were associated only with axicabtagene-ciloleucel therapy (n = 28 [1.6%], adj.ROR = 1.80 [1.24-2.62], IC025 >0). Atrial fibrillation (n = 55) was the leading tachyarrhythmia, followed by ventricular arrhythmias (n = 14). Tachyarrhythmias and VTEs were reported more often following axicabtagene-ciloleucel than tisagenlecleucel in an age- and sex-adjusted model (adj.ROR = 1.82 [1.04-3.18] and adj.ROR = 2.86 [1.18-6.93], respectively). Finally, the fatality rate of CPAEs was 30.9%.Conclusions: In this largest post-marketing study to date, the authors identified an association between CAR-T and various CPAEs, including tachyarrhythmias, cardiomyopathy, pericardial and pleural disorders, and VTEs. These findings should be considered in the multidisciplinary assessment for and monitoring of CAR-T therapy recipients. [ABSTRACT FROM AUTHOR]- Published
- 2021
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4. EE229 Cost-Effectiveness of Axicabtagene Ciloleucel and Tisagenlecleucel in 3L+ Relapsed/Refractory Large B-Cell Lymphoma in the United States Utilizing Real-World Evidence of Chimeric Antigen Receptor T-Cell Therapies.
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Locke, F.L., Ray, M., Bradford, R., Jones, C., Dieyi, C., Sun, F., Davies, N., Patel, A., and Oluwole, O.
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CHIMERIC antigen receptors , *T cells , *ANTIGEN receptors , *COST effectiveness , *B cells , *LYMPHOMAS , *RITUXIMAB - Published
- 2023
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5. Clinical practice: chimeric antigen receptor (CAR) T cells: a major breakthrough in the battle against cancer.
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Lundh, Stefan, Jung, In-Young, Dimitri, Alexander, Vora, Anish, Melenhorst, J. Joseph, Jadlowsky, Julie K., and Fraietta, Joseph A.
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CD19 antigen , *CHIMERIC antigen receptors , *T cells , *MANUFACTURING cells , *HEMATOLOGIC malignancies , *GENOME editing - Abstract
Chimeric antigen receptor (CAR) T cell therapy has come of age, offering a potentially curative option for patients who are refractory to standard anti-cancer treatments. The success of CAR T cell therapy in the setting of acute lymphoblastic leukemia and specific types of B cell lymphoma led to rapid regulatory approvals of CD19-directed CAR T cells, first in the United States and subsequently across the globe. Despite these major milestones in the field of immuno-oncology, growing experience with CAR T cells has also highlighted the major limitations of this strategy, namely challenges associated with manufacturing a bespoke patient–specific product, intrinsic immune cell defects leading to poor CAR T cell function as well as persistence, and/or tumor cell resistance resulting from loss or modulation of the targeted antigen. In addition, both on- and off-tumor immunotoxicities and the financial burden inherent in conventional cellular biomanufacturing often hamper the success of CAR T cell-based treatment approaches. Herein, we provide an overview of the opportunities and challenges related to the first form of gene transfer therapy to gain commercial approval in the United States. Ongoing advances in the areas of genetic engineering, precision genome editing, toxicity mitigation methods and cell manufacturing will improve the efficacy and safety of CAR T cells for hematologic malignancies and expand the use of this novel class of therapeutics to reach solid tumors. [ABSTRACT FROM AUTHOR]
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- 2020
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6. A New Approach to Treat Childhood Leukemia: Novartis' CAR-T Therapy.
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Tessema, Frazer A. and Darrow, Jonathan J.
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CHIMERIC antigen receptors , *LYMPHOBLASTIC leukemia in children , *T cells , *DRUG approval , *DISEASES in young adults , *DRUG prices , *NEUROTOXICOLOGY , *LEUKEMIA treatment , *CYTOKINES , *ANTIGENS , *ANTINEOPLASTIC agents , *CELL receptors , *GENETIC engineering , *INFECTION , *LYMPHOBLASTIC leukemia , *SYNDROMES , *TUMORS in children , *CHIMERISM , *INDIVIDUALIZED medicine , *ECONOMICS - Abstract
The article discusses the U.S. Food and Drug Administration's approval of the use of drug company Novartis AG's product tisagenlecleucel (Kymriah) to treat B-cell acute lymphoblastic leukemia (ALL) in children and young adults, and it mentions several chimeric antigen receptor T-cell (CAR-T) therapies. Neurotoxicity and acute cytokine release syndrome (cytokine storm) are examined, along with a risk evaluation and mitigation strategy (REMS) and drug prices in America.
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- 2017
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