Cellular immunology
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Cellular immunology · May 2021
A transgene-encoded truncated human epidermal growth factor receptor for depletion of anti- B-cell maturation antigen CAR-T cells.
Chimeric antigen receptor T cells (CAR-T) against B-cell maturation antigen (BCMA) has been used to treat multiple myeloma (MM). CAR-T cells co-expressing a truncated human EGFR (tEGFR) has been proposed for in vivo cell ablation. ⋯ We confirm that BCMA is a suitable target for CAR- T cells and tEGFR is a effective tool for cellular ablation.
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Cellular immunology · Nov 2019
ReviewThe promise of chimeric antigen receptor (CAR) T cell therapy in multiple myeloma.
A cure for multiple myeloma (MM), a malignancy of plasma cells, remains elusive. Nearly all myeloma patients will eventually relapse and develop resistance to currently available treatments. There is an unmet medical need to develop novel and effective therapies that can induce sustained responses. ⋯ In this review article, we provide an overview of the CAR constructs, the gene transfer vector systems, and approaches for T cell activation and expansion. We then summarize the outcomes of several early phase clinical trials of CAR T cell therapy in MM and the novel CAR T targets that are under development. Finally, we explore the potential mechanisms that result in disease relapse after CAR T therapy and propose future directions in CAR T therapy in MM.
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Cellular immunology · Dec 2018
ReviewThe challenges of checkpoint inhibition in the treatment of multiple myeloma.
Despite significant improvements in the overall survival of patients with multiple myeloma (MM) over the past 15 years, the disease remains incurable. Treatment options are limited for patients who have relapsed or are refractory to immunomodulatory drugs (IMiDs), proteasome inhibitors, and monoclonal antibodies. In these patients, immunotherapies such as checkpoint inhibitors, oncolytic vaccines, and chimeric antigen receptor (CAR) T cells provide a potentially effective alternative treatment. ⋯ These challenges highlight the need for a better understanding of immune dysregulation in myeloma patients, and the mechanisms of action of- and resistance to- checkpoint inhibitors. In this review, we summarize immune dysfunction in patients with MM, and review the preclinical and clinical data regarding checkpoint inhibitors in myeloma. We conclude by proposing strategies to improve the efficacy and safety of checkpoint inhibitors in this population.
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Cellular immunology · Oct 2018
Mivacurium induce mast cell activation and pseudo-allergic reactions via MAS-related G protein coupled receptor-X2.
Mivacurium is a non-depolarizing muscle relaxant and widely used as a short-acting anesthetic. Pseudo-allergic reactions to mivacurium occur when it is administered during perioperative anesthesia. These reactions may present a serious threat to the patient's life, particularly in children. ⋯ Mivacurium activated MRGPRX2 and triggered mast cell degranulation, leading to anaphylactoid reactions. However, mivacurium did not induce the release of other cytokines. Therefore, the targeting of MRGPRX2 can potentially block mivacurium-induced adverse drug effects, particularly pseudo-allergic reactions.