ArticleJournal for immunotherapy of cancer2023
Limited efficacy of APRIL CAR in patients with multiple myeloma indicate challenges in the use of natural ligands for CAR T-cell therapy.
Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT03287804 (A Single-Arm, Open-Label, Multi-Centre, Phase I/II Study Evaluating the Safety and Clinical Activity of AUTO2, a CAR T Cell Treatment Targeting BCMA and TACI, in Patients With Relapsed or Refractory Multiple Myeloma), which is not on this map. Cited by 27 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
A Single-Arm, Open-Label, Multi-Centre, Phase I/II Study Evaluating the Safety and Clinical Activity of AUTO2, a CAR T Cell Treatment Targeting BCMA and TACI, in Patients With Relapsed or Refractory Multiple Myeloma
Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- An Assessment of the Effectiveness and Safety of Chimeric Antigen Receptor T-Cell Therapy in Multiple Myeloma Patients with Relapsed or Refractory Disease: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2024Pooled it
- Multi-dimensional orchestration of binders for improved CAR-T immunotherapy.Cancer letters · 2026Review
- APRIL-driven BCMA/TACI dual-targeted ligand-drug conjugates for selective and potent therapy of multiple myeloma.Acta pharmaceutica Sinica. B · 2026Article
- Engineering a TACI × CD3 bispecific antibody to redirect T cells against multiple myeloma.Blood advances · 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
- 2025 Update of Cellular Immunotherapy for Plasma Cell Disorders.Turkish journal of haematology : official journal of Turkish Society of Haematology · 2026Review
- B7-H3 nanobody-based CAR T cells control multiple myeloma growth, while dual BCMA/B7-H3 CAR T cells overcome antigen escape.Journal of hematology & oncology · 2025Article
- ROR2-specific CAR T cells are effective against hematologic and solid tumors and well tolerated in mice.Cell reports. Medicine · 2025Article
- Tandem CAR-T cells targeting mesothelin and MUC16 overcome tumor heterogeneity by targeting one antigen at a time.Journal for immunotherapy of cancer · 2025Article
- Current Anti-Myeloma Chimeric Antigen Receptor-T Cells: Novel Targets and Methods.Balkan medical journal · 2025Review
- Expanding the CAR toolbox with high throughput screening strategies for CAR domain exploration: a comprehensive review.Journal for immunotherapy of cancer · 2025Review
- Increased functional potency of multi-edited CAR-T cells manufactured by a non-viral transfection system.Molecular therapy. Methods & clinical development · 2025Article
- Targeting BCMA in multiple myeloma: designs, challenges, and future directions.Cancer immunology, immunotherapy : CII · 2025Review
- Advances and prospects of RNA delivery nanoplatforms for cancer therapy.Acta pharmaceutica Sinica. B · 2025Review
- Unveiling causal immune cell-gene associations in multiple myeloma: insights from systematic reviews and Mendelian randomization analyses.Frontiers in medicine · 2025Article
- Are we there yet? CAR-T therapy in multiple myeloma.British journal of haematology · 2024Review
- Review
- Split-design approach enhances the therapeutic efficacy of ligand-based CAR-T cells against multiple B-cell malignancies.Nature communications · 2024Article
- Updates on CAR T cell therapy in multiple myeloma.Biomarker research · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
28 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundWe used a proliferating ligand (APRIL) to construct a ligand-based third generation chimeric antigen receptor (CAR) able to target two myeloma antigens, B-cell maturation antigen (BCMA) and transmembrane activator and CAML interactor.
methodsThe APRIL CAR was evaluated in a Phase 1 clinical trial (NCT03287804, AUTO2) in patients with relapsed, refractory multiple myeloma. Eleven patients received 13 doses, the first 15×10
resultsThe APRIL CAR was well tolerated. Five (45.5%) patients developed Grade 1 cytokine release syndrome and there was no neurotoxicity. However, responses were only observed in 45.5% patients (1×very good partial response, 3×partial response, 1×minimal response). Exploring the mechanistic basis for poor responses, we then compared the APRIL CAR to two other BCMA CARs in a series of in vitro assays, observing reduced interleukin-2 secretion and lack of sustained tumor control by APRIL CAR regardless of transduction method or co-stimulatory domain. There was also impaired interferon signaling of APRIL CAR and no evidence of autoactivation. Thus focusing on APRIL itself, we confirmed similar affinity to BCMA and protein stability in comparison to BCMA CAR binders but reduced binding by cell-expressed APRIL to soluble BCMA and reduced avidity to tumor cells. This indicated either suboptimal folding or stability of membrane-bound APRIL attenuating CAR activation.
conclusionsThe APRIL CAR was well tolerated, but the clinical responses observed in AUTO2 were disappointing. Subsequently, when comparing the APRIL CAR to other BCMA CARs, we observed in vitro functional deficiencies due to reduced target binding by cell-expressed ligand.
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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.