Evidence map›Paper›PMID 38463958›Full record

ArticlebioRxiv : the preprint server for biology2024

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

Corynn Kasap, Adila Izgutdina, Bonell Patiño-Escobar, Amrik Kang, Nikhil Chilakapati, Naomi Akagi, Haley Johnson, Tasfia Rashid, Juwita Werner, Abhilash Barpanda and 25 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. 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
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

0 citing papers in PubMed, 9 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

35 authors at 3 institutions in 2 countries.

Corynn KasapDept. of Medicine, Division of Hematology/Oncology, University of California, San Francisco, CA.ORCID 0000-0002-3667-8097
Adila IzgutdinaDept. of Laboratory Medicine, University of California, San Francisco, CA.
Bonell Patiño-EscobarDept. of Laboratory Medicine, University of California, San Francisco, CA.
Amrik KangDept. of Laboratory Medicine, University of California, San Francisco, CA.
Nikhil ChilakapatiDept. of Laboratory Medicine, University of California, San Francisco, CA.
Naomi AkagiDept. of Laboratory Medicine, University of California, San Francisco, CA.
Haley JohnsonDept. of Laboratory Medicine, University of California, San Francisco, CA.
Tasfia RashidDept. of Laboratory Medicine, University of California, San Francisco, CA.
Juwita WernerDept. of Pediatrics, Division of Oncology, University of California, San Francisco, CA.
Abhilash BarpandaDept. of Laboratory Medicine, University of California, San Francisco, CA.
Huimin GengDept. of Laboratory Medicine, University of California, San Francisco, CA.
Yu-Hsiu T LinDept. of Laboratory Medicine, University of California, San Francisco, CA.
Sham RampersaudDept. of Laboratory Medicine, University of California, San Francisco, CA.
Daniel Gil-AlósDept. of Laboratory Medicine, University of California, San Francisco, CA.
Amin SobhUniversity of Florida Health Cancer Center, The University of Florida Cancer and Genetics Research Complex, Gainesville, Florida.
Daphné Dupéré-RicherUniversity of Florida Health Cancer Center, The University of Florida Cancer and Genetics Research Complex, Gainesville, Florida.
Gianina WicaksonoDept. of Laboratory Medicine, University of California, San Francisco, CA.
K M Kawehi KeliiDept. of Laboratory Medicine, University of California, San Francisco, CA.
Radhika DalalDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA.
Emilio RamosDept. of Laboratory Medicine, University of California, San Francisco, CA.
Anjanaa VijayanarayananDept. of Laboratory Medicine, University of California, San Francisco, CA.
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.
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.
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.
Tanja KortemmeDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA.
Elliot StieglitzDept. of Pediatrics, Division of Oncology, University of California, San Francisco, CA.
Jonathan D LichtUniversity of Florida Health Cancer Center, The University of Florida Cancer and Genetics Research Complex, Gainesville, Florida.
William J KarlonDept. of Laboratory Medicine, University of California, San Francisco, CA.
Benjamin G BarwickDepartment of Hematology and Medical Oncology, Winship Cancer Institute, School of Medicine, Emory University, Atlanta, GA.
Arun P WiitaDept. of Laboratory Medicine, University of California, San Francisco, CA.ORCID 0000-0002-7465-6964
University of California, San Francisco · USEmory University · USUniversity of Florida Health · US

Funding

Translational InformaticsP30CA082103 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Jennifer Leigh Clarke · 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
Molecular Biophysics Training GrantT32GM149436 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Aashish Manglik · 2023 to 2026
$1.6M
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 CA082103NIGMS NIH HHS T32 GM141323NIGMS NIH HHS T32 GM142516NIGMS NIH HHS T32 GM149436
6 · The paper itself

Abstract

Despite the success of BCMA-targeting CAR-Ts in multiple myeloma, patients with high-risk cytogenetic features still 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 scFv-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.

Identifiers

PMID38463958
PMCPMC10925123
OpenAlexW4392243842

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.