The current standard of care in hematological malignancies has brought considerable clinical benefits to patients. However, important bottlenecks still limit optimal achievements following a current medical practice. The genetic complexity of the diseases and the heterogeneity of tumor clones cause difficulty in ensuring long-term efficacy of conventional treatments for most hematological disorders. Consequently, new treatment strategies are necessary to improve clinical outcomes. Chimeric antigen receptor T-cell (CAR T) immunotherapy opens a new path for targeted therapy of hematological malignancies. In this review, through a representative case study, we summarize the current experience of CAR T-cell therapy, the management of common side effects, the causative mechanisms of therapy resistance, and new strategies to improve the efficacy of CAR T-cell therapy.
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http://dx.doi.org/10.1007/s11684-021-0904-z | DOI Listing |
Mol Ther
January 2025
Brown Center for Immunotherapy. Indiana University School of Medicine. 975 W. Walnut St., IB554A, Indianapolis, IN 46202. Electronic address:
Chimeric Antigen Receptor (CAR) T cell therapy has revolutionized cancer treatment and is now being explored for other diseases, such as autoimmune disorders. While the tumor microenvironment (TME) in cancer is often immunosuppressive, in autoimmune diseases, the environment is typically inflammatory. Both environments can negatively impact CAR T cell survival: the former through direct suppression, hypoxia, and nutrient deprivation, and the latter through chronic T cell receptor (TCR) engagement, risking exhaustion.
View Article and Find Full Text PDFMol Ther
January 2025
Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology and School of Life Sciences, East China Normal University, Shanghai, China, 200241. Electronic address:
CAR T-cell therapy has achieved remarkable clinical success in treating hematological malignancies. However, its clinical efficacy in solid tumors is less satisfactory, partially due to poor in vivo expansion and limited persistence of CAR-T cells. Here, we demonstrated that the overexpression of glucocorticoid-induced tumor necrosis factor receptor-related protein ligand (GITRL) enhances the anti-tumor activity of CAR-T cells.
View Article and Find Full Text PDFBone Marrow Transplant
January 2025
Université de Franche-Comté, EFS, INSERM, UMR RIGHT, F-, 25000, Besançon, France.
The accessibility of CAR-T cells in centralized production models faces significant challenges, primarily stemming from logistical complexities and prohibitive costs. However, European Regulation EC No. 1394/2007 introduced a pivotal provision known as the hospital exemption.
View Article and Find Full Text PDFJ Immunother Cancer
January 2025
Cellular Immunotherapy Research Unit, Chulalongkorn University, Bangkok, Thailand
Background: B7 homolog 3 (B7-H3), an overexpressed antigen across multiple solid cancers, represents a promising target for CAR T cell therapy. This study investigated the expression of B7-H3 across various solid tumors and developed novel monoclonal antibodies (mAbs) targeting B7-H3 for CAR T cell therapy.
Methods: Expression of B7-H3 across various solid tumors was evaluated using RNA-seq data from TCGA, TARGET, and GTEx datasets and by flow cytometry staining.
Int Immunopharmacol
January 2025
Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041 Sichuan Province, People's Republic of China. Electronic address:
Chimeric antigen receptor T (CAR-T) cell therapy targeting B cell mature antigen (BCMA) has shown remarkable clinical benefits in treating multiple myeloma (MM). Bortezomib, a proteasome inhibitor approved as a first-line agent for MM for two decades, has demonstrated potent antitumor activity. In this study, we found that bortezomib treatment stabilizes the expression of BCMA and conceived the hypothesis that BCMA CAR-T therapy combined with bortezomib would enhance the anti-MM efficacy.
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