Evidence map›Paper›PMID 41072416›Full record

ArticleCancer cell2025

Developing SEMA4A-directed CAR T cells to overcome low BCMA antigen density in multiple myeloma.

Francesco Di Meo, Francesca Albano, Annamaria Cesarano, Yunfei Wang, Brandon Kale, Kenneth Shain, Ariosto Silva, Noriyoshi Kurihara, Hirofumi Tenshin, David Jellyman and 14 more

Abstract read
In one paragraph

Article in Cancer cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

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 literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors.

Francesco Di MeoDepartment of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Francesca AlbanoDepartment of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Annamaria CesaranoDepartment of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Yunfei WangDepartment of Clinical Science, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Brandon KaleDepartment of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Kenneth ShainDepartment of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Ariosto SilvaDepartment of Metabolism and Physiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Noriyoshi KuriharaDivision of Hematology/Oncology, Indiana University School of Medicine, Indianapolis, IN, USA.
Hirofumi TenshinDivision of Hematology/Oncology, Indiana University School of Medicine, Indianapolis, IN, USA.
David JellymanAntibody Technology, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Xiaofei SongDepartment of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Sasan GhaffariDepartment of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Hector MesaDepartment of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA.
Ben CreelanDepartment of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
Ciara FreemanDepartment of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Xiaohong ZhaoDepartment of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Mark B MeadsDepartment of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Paulo C RodriguezDepartment of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Silvia MarinoDepartment of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Frederick LockeDepartment of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Patrick HwuDepartment of Clinical Science, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
David RoodmanDivision of Hematology/Oncology, Indiana University School of Medicine, Indianapolis, IN, USA.
Jorge Mansilla-SotoDepartment of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; Department of Bioengineering, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Fabiana PernaDepartment of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; Department of Bioengineering, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. Electronic address: fabiana.perna@moffitt.org.

Funding

TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI John L. Cleveland · 1998 to 2026
$93.5M
Mitochondrial stress promotes immunosuppressive potential of myeloid subsets in tumorsR01CA273034 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI RODRIGUEZ, PAULO CESAR · 2022 to 2025
$1.9M
Identifying cell surface targets for innovative immunotherapy of Multiple MyelomaR37CA276939 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI Fabiana Perna · 2024 to 2026
$1.7M
NCI NIH HHS P30 CA076292NCI NIH HHS R01 CA273034NCI NIH HHS R37 CA276939
6 · The paper itself

Abstract

Chimeric antigen receptor (CAR) T cell therapy targeting B cell maturation antigen (BCMA) for multiple myeloma (MM) is effective, but relapses associated with low-to-negative BCMA expression are common, indicating the need for additional targets. We quantitatively profile antigen density in a cohort of patients relapsed after BCMA CAR T therapy, showing high number of SEMA4A molecules/cell where BCMA density is low. SEMA4A deletion limits MM cell growth, migration, tissue infiltration, and osteoclast formation, while extending mouse survival. We generate monoclonal antibodies targeting SEMA4A-extracellular domain for CAR construction, screen engineered T cells for expansion, cytokine release, and cytotoxicity against MM cells. Lead constructs lack reactivity against normal non-hematopoietic tissues. SEMA4A CAR T cells show superior efficacy than BCMA CAR T cells eliminating patient-derived BCMA

Indexed as

B-Cell Maturation AntigenImmunotherapy, AdoptiveMultiple MyelomaReceptors, Chimeric AntigenSemaphorinsT-LymphocytesAnimalsCell Line, TumorHumansMiceXenograft Model Antitumor AssaysB-Cell Maturation AntigenReceptors, Chimeric AntigenSEMA4A protein, humanSemaphorinsantibody developmentantigen densityantigen escapeBCMACAR T cell therapyMultiple Myelomamyeloma biologyrelapseSEMA4Atarget identification

Identifiers

PMID41072416
PMCPMC12614569

What OpenQuestion holds

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Registered trials

None linked

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.