Evidence map›Paper›PMID 40359480›Full record

ArticleBlood2025

Targeting high-risk multiple myeloma genotypes with optimized anti-CD70 CAR T cells.

Corynn Kasap, Adila Izgutdina, Bonell Patiño-Escobar, Amrik S Kang, Nikhil Chilakapati, Naomi Akagi, Ananya Manoj, Haley Johnson, Tasfia Rashid, Juwita Werner and 35 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Blood, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Targets for CAR Therapy in Multiple Myeloma.International journal of molecular sciences · 2025
    Review
  9. Review
  10. Review
  11. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

45 authors.

Corynn KasapDivision of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA.ORCID 0000-0002-3667-8097
Adila IzgutdinaDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA.ORCID 0000-0002-3296-3261
Bonell Patiño-EscobarDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA.ORCID 0000-0003-2622-4822
Amrik S KangDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA.ORCID 0000-0003-0445-5654
Nikhil ChilakapatiDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA.ORCID 0009-0004-3456-8144
Naomi AkagiDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA.
Ananya ManojDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA.ORCID 0009-0000-5578-4429
Haley JohnsonDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA.ORCID 0009-0002-1527-7910
Tasfia RashidDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA.
Juwita WernerDivision of Oncology, Department of Pediatrics, University of California San Francisco, San Francisco, CA.ORCID 0009-0007-9635-2519
Abhilash BarpandaDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA.ORCID 0000-0001-8158-4949
Huimin GengDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA.
Yu-Hsiu T LinDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA.
Sham RampersaudDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA.ORCID 0000-0001-7473-4144
Daniel Gil-AlósDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA.ORCID 0009-0002-8504-2842
Amin SobhDivision of Hematology/Oncology, University of Florida Health Cancer Center, Gainesville, FL.
Daphné Dupéré-RicherDivision of Hematology/Oncology, University of Florida Health Cancer Center, Gainesville, FL.
Adolfo AlemanDepartment of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY.ORCID 0000-0002-8884-2100
Gianina WicaksonoDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA.ORCID 0000-0001-5524-0245
K M Kawehi KeliiDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA.
Radhika DalalDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA.ORCID 0000-0002-7128-5635
Emilio RamosDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA.
Anjanaa VijayanarayananDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA.
Kiran LakhaniDepartment of Hematology and Medical Oncology, Winship Cancer Institute, School of Medicine, Emory University, Atlanta, GA.
Fernando SalangsangHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA.
Paul PhojanakongHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA.
Juan Antonio Camara SerranoHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA.ORCID 0000-0001-7494-1127
Ons ZakraouiHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA.
Isa TariqHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA.
Ajai ChariDivision of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA.
Alfred ChungDivision of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA.ORCID 0000-0003-0196-5456
Anupama D KumarDivision of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA.
Thomas G MartinDivision of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA.
Jeffrey WolfDivision of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA.
Sandy W WongDivision of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA.
Veronica SteriHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA.
Mala ShanmugamDepartment of Hematology and Medical Oncology, Winship Cancer Institute, School of Medicine, Emory University, Atlanta, GA.
Lawrence H BoiseDepartment of Hematology and Medical Oncology, Winship Cancer Institute, School of Medicine, Emory University, Atlanta, GA.ORCID 0000-0001-9436-8815
Tanja KortemmeDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA.
Samir ParekhDepartment of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY.
Elliot StieglitzDivision of Oncology, Department of Pediatrics, University of California San Francisco, San Francisco, CA.ORCID 0000-0001-7032-4623
Jonathan D LichtDivision of Hematology/Oncology, University of Florida Health Cancer Center, Gainesville, FL.ORCID 0000-0002-3942-1369
William J KarlonDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA.
Benjamin G BarwickDepartment of Hematology and Medical Oncology, Winship Cancer Institute, School of Medicine, Emory University, Atlanta, GA.ORCID 0000-0001-9810-3566
Arun P WiitaDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA.ORCID 0000-0002-7465-6964

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
Translational InformaticsP30CA082103 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Alan Ashworth · 1999 to 2026
$209.7M
Medical Scientist Training Program (T32 NRSA Training Grant)T32GM141323 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Aimee Kao · 2021 to 2026
$10.5M
Pharmaceutical Sciences and PharmacogenomicsT32GM142516 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Su Guo · 2022 to 2026
$2.4M
Multi-functional cellular therapies to overcome tumor heterogeneity and limit toxicity in acute myeloid leukemiaF32CA271812 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KASAP, CORYNN · 2023 to 2024
$174k
NCI NIH HHS F32 CA271812NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA082103NIGMS NIH HHS T32 GM141323NIGMS NIH HHS T32 GM142516
6 · The paper itself

Abstract

abstractDespite the success of B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T cells (CAR-Ts) in multiple myeloma, patients with high-risk cytogenetic features continue to relapse most quickly and are in urgent need of additional therapeutic options. Here, we identify CD70, widely recognized as a favorable immunotherapy target in other cancers, as a specifically upregulated cell surface antigen in high-risk myeloma tumors. We use a structure-guided design to define a CD27-based anti-CD70 CAR-T design that outperforms all tested single-chain variable fragment-based CARs, leading to >80-fold improved CAR-T expansion in vivo. Epigenetic analysis via machine learning predicts key transcription factors and transcriptional networks driving CD70 upregulation in high-risk myeloma. Dual-targeting CAR-Ts against either CD70 or BCMA demonstrate a potential strategy to avoid antigen escape-mediated resistance. Together, these findings support the promise of targeting CD70 with optimized CAR-Ts in myeloma as well as future clinical translation of this approach.

Indexed as

CD27 LigandImmunotherapy, AdoptiveMultiple MyelomaB-Cell Maturation AntigenEpigenomicsGene Expression Regulation, NeoplasticGene Regulatory NetworksHumansMachine LearningMolecular Targeted TherapyReceptors, Chimeric AntigenTranscription FactorsTumor EscapeUp-RegulationB-Cell Maturation AntigenCD27 LigandCD70 protein, humanReceptors, Chimeric AntigenTranscription Factors

Identifiers

PMID40359480
PMCPMC12783522

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.