ArticleBlood advances2019
Rational design of a trimeric APRIL-based CAR-binding domain enables efficient targeting of multiple myeloma.
Article in Blood advances, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
80 citing papers in PubMed, 2 syntheses or guidelines pooled it, 108 citations in OpenAlex.
- Effectiveness and safety of anti-BCMA chimeric antigen receptor T-cell treatment in relapsed/refractory multiple myeloma: a comprehensive review and meta-analysis of prospective clinical trials.Frontiers in pharmacology · 2023Pooled it
- Ligand-based CAR-T cell: Different strategies to drive T cells in future new treatments.Frontiers in immunology · 2022Pooled it
- Dual targeting of BCMA and GPRC5D with the trispecific antibody ramantamig addresses antigenic heterogeneity in myeloma.HemaSphere · 2026Article
- APRIL-driven BCMA/TACI dual-targeted ligand-drug conjugates for selective and potent therapy of multiple myeloma.Acta pharmaceutica Sinica. B · 2026Article
- Design optimization of antibody-ligand motifs to enhance CAR-T redirection activity against solid tumors.Cell reports. Medicine · 2026Article
- CAR-modified marrow infiltrating lymphocytes efficiently target malignant plasma cells with very low antigen density.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Bridging biomaterials and immunotherapy: hydrogel strategies for next-generation CAR-T cell treatment.Stem cell research & therapy · 2026Review
- The rise and future of peptide-based antimicrobials.Journal of microbiology (Seoul, Korea) · 2026Review
- Decoding signaling architectures: CAR versus TCR dynamics in solid tumor immunotherapy.Acta biochimica et biophysica Sinica · 2026Review
- BAFF-based trifunctional T-cell engagers trigger robust tumor immunity against B-cell malignancies.Protein & cell · 2025Article
- Review
- Fine tuning towards the next generation of engineered T cells.Nature biomedical engineering · 2025Review
- Barriers and solutions for CAR-T therapy in solid tumors.Cancer gene therapy · 2025Review
- Targets for CAR Therapy in Multiple Myeloma.International journal of molecular sciences · 2025Review
- Targeting BCMA in multiple myeloma: designs, challenges, and future directions.Cancer immunology, immunotherapy : CII · 2025Review
- Engineering the next generation of CAR T- cells: precision modifications, logic gates and universal strategies to overcome exhaustion and tumor resistance.Frontiers in oncology · 2025Review
- Non-signaling but all important: how the linker, hinge, and transmembrane domains in the CAR hold it all together.Frontiers in immunology · 2025Review
- The development and application of chimeric antigen receptor natural killer (CAR-NK) cells for cancer therapy: current state, challenges and emerging therapeutic advances.Experimental hematology & oncology · 2024Review
- Are we there yet? CAR-T therapy in multiple myeloma.British journal of haematology · 2024Review
- Split-design approach enhances the therapeutic efficacy of ligand-based CAR-T cells against multiple B-cell malignancies.Nature communications · 2024Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 5 institutions in 3 countries.
Funding
Abstract
Chimeric antigen receptor (CAR) T cells (CARTs) have shown tremendous potential for the treatment of certain B-cell malignancies, including patients with relapsed/refractory multiple myeloma (MM). Targeting the B-cell maturation antigen (BCMA) has produced the most promising results for CART therapy of MM to date, but not all remissions are sustained. Emergence of BCMA escape variants has been reported under the selective pressure of monospecific anti-BCMA CART treatment. Thus, there is a clinical need for continuous improvement of CART therapies for MM. Here, we show that a novel trimeric APRIL (a proliferation-inducing ligand)-based CAR efficiently targets both BCMA+ and BCMA- MM. Modeled after the natural ligand-receptor pair, APRIL-based CARs allow for bispecific targeting of the MM-associated antigens BCMA and transmembrane activator and CAML interactor (TACI). However, natural ligands as CAR antigen-binding domains may require further engineering to promote optimal binding and multimerization to adequately trigger T-cell activation. We found that using a trimeric rather than a monomeric APRIL format as the antigen-binding domain enhanced binding to BCMA and TACI and CART activity against MM in vitro and in vivo. Dual-specific, trimeric APRIL-based CAR are a promising therapeutic approach for MM with potential for preventing and treating BCMA escape.
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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.