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T-cell redirecting therapies such as chimeric antigen receptor T-cells and bispecific antibodies, are emerging as a novel class of immunotherapeutic agents for treatment of relapsed refractory multiple myeloma (MM). Their use is associated with an increased risk of infectious adverse events, fostered by cytopenias, hypogammaglobulinemia and T-cell exhaustion. Multiple ongoing clinical trials and real-world studies are investigating safety of T-cell therapy, highlighting the need for strategies to prevent and monitor the risk of infection. Recommended measures for risk mitigation include intravenous immunoglobulin supplementation, adequate prophylaxis therapy, vaccination and careful assessment for early diagnosis and treatment of infection. Here, we summarize available data on the risk of infections with approved and under development T-cell redirecting therapies for the treatment of MM.
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http://dx.doi.org/10.1016/j.clml.2024.05.002 | DOI Listing |
Br J Haematol
July 2025
Division of Hematology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA.
Mol Ther Methods Clin Dev
September 2025
UMR 1098 RIGHT INSERM/Etablissement Français du Sang Bourgogne Franche-Comté/Université Marie et Louis Pasteur, 25000 Besançon, France.
Despite the clinical success of redirected T cells in the setting of cancer adoptive cell immunotherapy, patients may exhibit resistance to treatment, resulting in uncontrolled disease and relapses. This phenomenon partly relies on impaired -produced T cell metabolic fitness, including a decreased respiratory reserve, as well as a greater sensitivity to tumor-mediated metabolic stress. To improve the respiratory capacity of cultured T cells, we sought to target the nicotinamide adenine dinucleotide/sirtuine-1/reactive oxygen species (ROS) axis through supplementation of culture medium with resveratrol.
View Article and Find Full Text PDFUnlabelled: Currently approved type 1 diabetes (T1D) immunotherapies broadly target T cells and delay but do not fully prevent diabetes development, highlighting the need for more selective targets. Anti-insulin germinal center B cells are uniquely able to present pathogenic insulin epitopes and drive anti-insulin T cells to adopt a T follicular helper fate. T cell expression of BCL6, a key transcriptional repressor in the germinal center response, is essential for spontaneous diabetes in non-obese diabetic (NOD) mice.
View Article and Find Full Text PDFBlood Cancer Discov
September 2025
Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Genomic antigen loss is a recurring mechanism of resistance to chimeric antigen receptor T-cell (CAR-T) and T-cell engagers (TCE) in relapsed/refractory multiple myeloma (RRMM). Yet, it remains unclear whether these events are acquired under treatment or merely selected from pre-existing, undetectable clones. By leveraging chemotherapy mutational signatures as temporal barcodes within whole genome sequencing data, we could time genomic antigen escape in 4 out of 11 RRMM patients.
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September 2025
University of Minnesota, Minneapolis, Minnesota, United States.
The significance of endogenous immune surveillance in acute lymphoblastic leukemia (ALL) remains controversial. Using clinical B-ALL samples and a novel mouse model, we show that neoantigen-specific CD4+ T-cells are induced to adopt type-1 regulatory (Tr1) function in the leukemia microenvironment. Tr1s then inhibit cytotoxic CD8+ T-cells, preventing effective leukemia clearance.
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