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| http://dx.doi.org/10.18632/oncotarget.25688 | DOI Listing |
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Expanded tumor-associated polymorphonuclear myeloid-derived suppressor cells in Waldenstrom macroglobulinemia display immune suppressive activity.
Blood Cancer J
December 2024
Division of Hematology and Internal Medicine Mayo Clinic, Rochester, MN, USA.
The role of the bone marrow (BM) microenvironment in regulating the antitumor immune response in Waldenstrom macroglobulinemia (WM) remains poorly understood. Here we transcriptionally and phenotypically profiled non-malignant (CD19 CD138) BM cells from WM patients with a focus on myeloid derived suppressive cells (MDSCs) to provide a deeper understanding of their role in WM. We found that HLA-DRCD11bCD33 MDSCs were significantly increased in WM patients as compared to normal controls, with an expansion of predominantly polymorphonuclear (PMN)-MDSCs.
View Article and Find Full Text PDFPreclinical development of three novel CARs targeting CD79b for the treatment of non-Hodgkin's lymphoma and characterization of the loss of the target antigen.
J Immunother Cancer
December 2024
Department of Experimental Hematology, Health Research Institute of the Jimenez Diaz Foundation, UAM, Madrid, Spain, UAM, Madrid, Spain
Background: Infusion of T cells modified with a chimeric antigen receptor (CAR) targeting CD19 has achieved exceptional responses in patients with non-Hodgkin's lymphoma (NHL), which led to the approval of CAR targeting CD19 (CART19) (Axi-cel and Liso-cel) as second line of treatment for adult patients with relapsed/refractory NHL. Unfortunately, 60% of patients still relapse after CART19 due to either a loss of expression of the target antigen (CD19) in the tumor cell, observed in 27% of relapsed patients, a limited CAR-T persistence, and additional mechanisms, including the suppression of the tumor microenvironment. Clinic strategies to prevent target antigen loss include sequential treatment with CARs directed at CD20 or CD22, which have caused loss of the second antigen, suggesting targeting other antigens less prone to disappear.
View Article and Find Full Text PDFCharacterization of Freshly Isolated Human Peripheral Blood B Cells, Monocytes, CD4+ and CD8+ T Cells, and Skin Mast Cells by Quantitative Transcriptomics.
Int J Mol Sci
December 2024
Department of Cell and Molecular Biology, Uppsala University, The Biomedical Center, Box 596, SE-751 24 Uppsala, Sweden.
Quantitative transcriptomics offers a new way to obtain a detailed picture of freshly isolated cells. By direct isolation, the cells are unaffected by in vitro culture, and the isolation at cold temperatures maintains the cells relatively unaltered in phenotype by avoiding activation through receptor cross-linking or plastic adherence. Simultaneous analysis of several cell types provides the opportunity to obtain detailed pictures of transcriptomic differences between them.
View Article and Find Full Text PDFCAR-based cell therapies for systemic lupus erythematosus.
Chin Med J (Engl)
December 2024
Department of Rheumatology, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai 200127, China.
The remarkable efficacy of chimeric antigen receptor (CAR) T cell therapy in hematological malignancies has provided a solid basis for the therapeutic concept, wherein specific pathogenic cell populations can be eradicated by means of targeted recognition. During the past few years, CAR-based cell therapies have been extensively investigated in preclinical and clinical research across various non-tumor diseases, with particular emphasis in the treatment of autoimmune diseases (ADs), yielding significant advancements. The recent deployment of CD19-directed CAR T cells has induced long-lasting, drug-free remission in patients with systemic lupus erythematosus (SLE) and other systemic AD, alongside a more profound immune reconstruction of B cell repertoire compared with conventional immunosuppressive agents and B cell-targeting biologics.
View Article and Find Full Text PDFLisocabtagene Maraleucel for Relapsed/Refractory Large B-Cell Lymphoma: A Cell Therapy Consortium Real-World Analysis.
Blood Adv
December 2024
University of Pennsylvania, Philadelphia, Pennsylvania, United States.
Lisocabtagene maraleucel (liso-cel) is an autologous CD19-directed CAR T cell therapy approved for the treatment of relapsed/refractory large B-cell lymphoma (LBCL). We present a multicenter retrospective study evaluating safety, efficacy, and resource utilization of liso-cel in the standard-of-care setting. Patients received commercial liso-cel at 7 US medical centers and patient selection, toxicity management, and disease assessment followed institutional practices.
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