Publications by authors named "N Leblay"
Adoptive T-cell therapy is a promising therapy for multiple myeloma (MM), but its efficacy hinges on understanding the relevant biologic and predictive markers of response. B-cell maturation antigen (BCMA) is a key target antigen in MM with active development of multiple anti-BCMA T-cell engagers (TCEs) and chimeric antigen receptor T-cell therapies. The regulation of surface BCMA expression by MM cells, which leads to shedding of soluble BCMA (sBCMA), has triggered debate about the significance of sBCMA as a predictive marker and its potential impact on treatment outcomes.
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- Research shows a correlation between the gut microbiome and the effectiveness of cancer immunotherapy, specifically for CAR T cell patients.
- The study identifies pentanoate, a metabolite from commensal bacteria, as a key factor that enhances patient survival by improving CAR T cell performance in challenging tumor environments.
- Findings suggest that incorporating microbial metabolites like pentanoate into CAR T cell manufacturing can exploit metabolic pathways and epigenetic changes to enhance treatment outcomes.
Article Synopsis
- Recent insights into the adaptive and innate immune systems' roles in cancers like multiple myeloma (MM) have spurred the creation of new immune-based treatments.
- Key targets for these therapies include proteins like B cell maturation antigen (BCMA), GPRC5D, and FcRL5, which are found on plasma cells and have shown promise in patients with tough-to-treat MM.
- Although some immunotherapies, such as antibody-drug conjugates and CAR T cells, have been approved since 2020, not all patients respond, and resistance to these treatments is common, prompting discussions on strategies to enhance effectiveness and manage resistance.
Unlabelled: Immunomodulatory drugs (IMiD) are a backbone therapy for multiple myeloma (MM). Despite their efficacy, most patients develop resistance, and the mechanisms are not fully defined. Here, we show that IMiD responses are directed by IMiD-dependent degradation of IKZF1 and IKZF3 that bind to enhancers necessary to sustain the expression of MYC and other myeloma oncogenes.
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- The translocation t(11;14) is found in 20% of people with multiple myeloma (MM) and makes a specific protein called CCND1 more active.
- Many of these MM cells are sensitive to the drug venetoclax, which targets another protein called BCL2, but the reasons for this are not fully understood.
- In this study, scientists used special techniques to look at the genes in t(11;14) MM cells, finding that they have a B-cell-like signature and that changes in this signature are related to becoming resistant to venetoclax treatment.