ArticleNature communications2026
The EF1α promoter of cilta-cel drives a highly effective GZMK
Kevin Herrera, Sneha Mitra, Yuqing Sun, Kimberly Lucero, Kristin A Singh, Kevin Chen, Meril Takizawa, Gunjan L Shah, Sergio Giralt, Jae H Park and 6 more
Abstract read
In one paragraphArticle in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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.
2 · The registryThe 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
3 · Its place in the literatureWho cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
4 · The recordCorrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
5 · Who and what moneyAuthors and funding
16 authors.
Kevin Herrera *Division of Hematologic Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Sneha Mitra *Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.ORCID 0000-0002-7718-8721 Yuqing SunDivision of Hematologic Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Kimberly LuceroDivision of Hematologic Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Kristin A SinghDivision of Hematologic Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Kevin ChenAntitumor Assessment Core Facility, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.
Meril TakizawaSingle Cell Analytics Innovation Lab, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Gunjan L ShahDivision of Hematologic Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0002-9977-0456 Sergio GiraltDivision of Hematologic Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Jae H ParkDivision of Hematologic Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0002-2903-5130 Saad Z UsmaniDivision of Hematologic Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0002-5484-8731 Ronan ChaligneSingle Cell Analytics Innovation Lab, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0003-4332-3291 Elisa de StanchinaAntitumor Assessment Core Facility, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.
Sham MailankodyDivision of Hematologic Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0002-2815-9561 Christina S LeslieComputational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.ORCID 0000-0002-4571-5910 Karlo PericaDivision of Hematologic Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. pericak@mskcc.org.ORCID 0000-0002-3595-7596 Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MU.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) P30 CA008748
6 · The paper itselfAbstract
Ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel) are approved BCMA-directed chimeric antigen receptor (CAR) T cells approved for the treatment of multiple myeloma. Although the higher efficacy of cilta-cel compared to ide-cel may be related to its unique nanobody binding domain, the constructs also differ in their use of EF1α and MND promoters, respectively, to drive CAR expression. To elucidate the basis of cilta-cel's efficacy, we analyzed CAR T cells from 87 patients with multiple myeloma (50 cilta-cel, 37 ide-cel) using flow cytometry and single-cell multi-omics. Cilta-cel showed a 10- fold higher peak expansion and greater persistence, driven by an inflammatory GZMK⁺ T cell subset marked by EOMES expression and motif accessibility, but not exhaustion profile. In myeloma xenograft models, the EF1α promoter in cilta-cel, rather than binding domain, recapitulated increased tumor control, enhanced expansion, and GZMK transcriptional profile compared with the MND promoter (ide-cel). These findings suggest that the efficacy of cilta-cel is linked to an EF1α-driven GZMK⁺ transcriptional trajectory that supports both persistence and effector function.
Indexed as
Multiple MyelomaPeptide Elongation Factor 1Promoter Regions, GeneticReceptors, Chimeric AntigenAnimalsCell Line, TumorHumansImmunotherapy, AdoptiveMiceT-LymphocytesTranscription, GeneticXenograft Model Antitumor AssaysPeptide Elongation Factor 1Receptors, Chimeric Antigen
Identifiers
PMID42901918
PMCPMC13683350
What OpenQuestion holds
Textmetadata
Read underepoch 390