Evidence map›Paper›PMID 40739330›Full record

ArticleLeukemia2025

Combining MCL-1 inhibition and CD37-directed chimeric antigen receptor T cells as an effective strategy to target T-cell lymphoma.

Tayla B Heavican-Foral, Felix Korell, Irene Scarfò, Caroline R M Wiggers, Allen Thayakumar B, Zachary Eisenbies, Foster Powers, Justin Hegel, Jianlin Liu, Steffen Kulp and 8 more

Abstract read
In one paragraph

Article in Leukemia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
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

18 authors.

Tayla B Heavican-ForalPediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0002-8384-6217
Felix KorellCancer Center, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0001-7699-7212
Irene ScarfòCancer Center, Massachusetts General Hospital, Boston, MA, USA.
Caroline R M WiggersPediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0001-6633-1468
Allen Thayakumar BPediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0001-7664-5030
Zachary EisenbiesPediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Foster PowersMedical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0009-0000-8276-4124
Justin HegelPediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0009-0004-7091-8578
Jianlin LiuPediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Steffen KulpMedical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0009-0001-9400-690X
Harrison SilvaCancer Center, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0003-4386-0847
Gongwei WuMedical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0002-2509-2381
Anthony LetaiMedical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0002-1993-9013
Kimberly StegmaierPediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0003-0218-7895
Jens G LohrMedical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0003-3486-2445
David M WeinstockMedical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0002-8724-3907
Marcela V Maus *Harvard Medical School, Boston, MA, USA. mvmaus@mgh.harvard.edu.ORCID 0000-0002-7578-0393
Birgit Knoechel *Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. birgit_knoechel@dfci.harvard.edu.ORCID 0000-0002-8040-0535

Funding

Targeting oncogenic TCR signaling in PTCLP01CA233412 · NCI · DANA-FARBER CANCER INST · PI KNOECHEL, BIRGIT · 2019 to 2023
$8.7M
Integrating Transforming Approaches to Identify and Target New Vulnerabilities in CancerR35CA210030 · NCI · DANA-FARBER CANCER INST · PI STEGMAIER, KIMBERLY · 2016 to 2022
$7.3M
Reading mitochondrial apoptotic signaling to identify active cancer therapeuticsR35CA242427 · NCI · DANA-FARBER CANCER INST · PI LETAI, ANTHONY G · 2019 to 2025
$7.0M
Understanding and manipulating programmed cell death (PCD) pathways to facilitate lymphoid tumor killing by CAR T cellsR01CA249062 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI MAUS, MARCELA VALDERRAMA · 2021 to 2025
$3.5M
Targeting High-Risk Lymphoid NeoplasmsR35CA231958 · NCI · DANA-FARBER CANCER INST · PI WEINSTOCK, DAVID MARC · 2019 to 2021
$2.9M
Mechanisms of immune evasion in T-cell acute lymphoblastic leukemia and its therapeutic implicationsR01CA249185 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI KNOECHEL, BIRGIT · 2021 to 2025
$1.9M
Liquid Biopsy in Myeloma to Inform Outcome and Treatment DecisionsR37CA276044 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Jens G Lohr · 2023 to 2026
$1.5M
NCI NIH HHS P01 CA233412NCI NIH HHS R01 CA249062NCI NIH HHS R01 CA249185NCI NIH HHS R35 CA210030NCI NIH HHS R35 CA231958NCI NIH HHS R35 CA242427NCI NIH HHS R37 CA276044
6 · The paper itself

Abstract

Chimeric antigen receptor (CAR) T cell therapy has not yet been realized for T-cell lymphomas (TCL), partially due to challenges in identifying tumor-specific antigens. We previously reported selective expression of CD37 on malignant T cells in a subset of TCL. Herein, we demonstrate CAR-37 T cells specifically target CD37-positive TCL in part by activating the intrinsic apoptotic pathway. To maximize therapeutic index, we identified selective/targetable BH3 dependences in individual TCL models and combined with CAR-37 T cells. We show that BH3 mimetics do not alter CD37 antigen binding capacity on TCL and have minimal effects on CAR-37 T-cell phenotype or function. In TCL models with dependence on MCL-1, combining CAR-37 T cells and the MCL-1 inhibitor AZD5991 increases anti-TCL response and prolongs survival of xenografted mice. These findings suggest that personalized selection of BH3 mimetic/CAR-T combinations could maximize the therapeutic index for patients with TCL and possibly other diseases.

Indexed as

Antineoplastic AgentsImmunotherapy, AdoptiveLymphoma, T-CellMyeloid Cell Leukemia Sequence 1 ProteinAnimalsAntigens, NeoplasmCell Line, TumorHumansMacrocyclic CompoundsMiceTetraspaninsXenograft Model Antitumor AssaysAntigens, NeoplasmAntineoplastic AgentsAZD5991CD37 protein, humanMacrocyclic CompoundsMCL1 protein, humanMyeloid Cell Leukemia Sequence 1 ProteinTetraspanins

Identifiers

PMID40739330
PMCPMC12463675

What OpenQuestion holds

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Registered trials

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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.