ArticleHaematologica2023
All-trans retinoic acid works synergistically with the γ-secretase inhibitor crenigacestat to augment BCMA on multiple myeloma and the efficacy of BCMA-CAR T cells.
Article in Haematologica, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06536413 (Phase IB/II Study Combining All-Trans Retinoic Acid), which is not on this map. Cited by 23 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase IB/II Study Combining All-Trans Retinoic Acid (ATRA) With Carfilzomib Based Therapy in Plasma Cell Myeloma Patients Refractory to Carfilzomib
Who cites it
23 citing papers in PubMed, 30 citations in OpenAlex.
- Mechanisms, optimization strategies, and salvage options for CAR-T cell therapy.Biomarker research · 2026Review
- Bridging preclinical development and clinical manufacturing: a translational GMP-Platform for lentiviral vector production in academic CAR T-Cell therapy.Journal of translational medicine · 2026Article
- Overcoming resistance in CD44-overexpressing myeloma through combination therapy with ATRA, bortezomib, and NK cells.Cancer immunology, immunotherapy : CII · 2026Article
- Dynamics of BCMA expression in patients with relapsed/refractory multiple myeloma receiving BCMA-directed CAR-T therapy.Blood cancer journal · 2026Article
- Targeting endosomal trafficking-mediated antigen escape to resensitize myeloma to CAR-T therapy.Journal for immunotherapy of cancer · 2026Article
- CC-DenseSTORM: deep learning enables colorimetry camera-based simultaneous two-color single-molecule localization microscopy with dense emitters.Biomedical optics express · 2026Article
- Single-molecule localization microscopy reveals the molecular organization of endogenous membrane receptors.Science advances · 2026Article
- Myeloid-derived suppressor cells in multiple myeloma: mechanistic insights and therapeutic implications.Frontiers in immunology · 2026Review
- Nanomedicine-Empowered CAR-T Therapy for Multiple Myeloma: Toward Programmable, Durable, and Precision Immunotherapy.International journal of nanomedicine · 2026Review
- ROR2-specific CAR T cells are effective against hematologic and solid tumors and well tolerated in mice.Cell reports. Medicine · 2025Article
- Mechanisms of Resistance to CAR T-Cells and How to Overcome Them.Methods and protocols · 2025Review
- Enhancing plasmacytoid dendritic cell functionality withMolecular therapy. Oncology · 2025Article
- Strategies for salvage therapy post CAR-T therapy failure in refractory/relapsed multiple myeloma patients.Frontiers in pharmacology · 2025Review
- Accelerating CAR-T Cell Therapies with Small-Molecule Inhibitors.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Kinetics of Nirogacestat-Mediated Increases in B-cell Maturation Antigen on Plasma Cells Inform Therapeutic Combinations in Multiple Myeloma.Cancer research communications · 2024Article
- Single-cell multiomic dissection of response and resistance to chimeric antigen receptor T cells against BCMA in relapsed multiple myeloma.Nature cancer · 2024Article
- Secretase promotes AD progression: simultaneously cleave Notch and APP.Frontiers in aging neuroscience · 2024Review
- All-trans retinoic acid in hematologic disorders: not just acute promyelocytic leukemia.Frontiers in pharmacology · 2024Review
- CAR-T Therapy in Relapsed Refractory Multiple Myeloma.Current medicinal chemistry · 2024Review
- CARs and Drugs: Pharmacological Ways of Boosting CAR-T-Cell Therapy.International journal of molecular sciences · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
B-cell maturation antigen (BCMA) is the lead antigen for chimeric antigen receptor (CAR) T-cell therapy in multiple myeloma (MM). A challenge is inter- and intra-patient heterogeneity in BCMA expression on MM cells and BCMA downmodulation under therapeutic pressure. Accordingly, there is a desire to augment and sustain BCMA expression on MM cells in patients that receive BCMA-CAR T-cell therapy. We used all-trans retinoic acid (ATRA) to augment BCMA expression on MM cells and to increase the efficacy of BCMA-CAR T cells in pre-clinical models. We show that ATRA treatment leads to an increase in BCMA transcripts by quantitative reverse transcription polymerase chain reaction and an increase in BCMA protein expression by flow cytometry in MM cell lines and primary MM cells. Analyses with super-resolution microscopy confirmed increased BCMA protein expression and revealed an even distribution of non-clustered BCMA molecules on the MM cell membrane after ATRA treatment. The enhanced BCMA expression on MM cells after ATRA treatment led to enhanced cytolysis, cytokine secretion and proliferation of BCMA-CAR T cells in vitro, and increased efficacy of BCMA-CAR T-cell therapy in a murine xenograft model of MM in vivo (NSG/MM.1S). Combination treatment of MM cells with ATRA and the γ- secretase inhibitor crenigacestat further enhanced BCMA expression and the efficacy of BCMA-CAR T-cell therapy in vitro and in vivo. Taken together, the data show that ATRA treatment leads to enhanced BCMA expression on MM cells and consecutively, enhanced reactivity of BCMA-CAR T cells. The data support the clinical evaluation of ATRA in combination with BCMA-CAR T-cell therapy and potentially, other BCMA-directed immunotherapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.