Evidence map›Paper›PMID 39863931›Full record

ReviewMolecular therapy : the journal of the American Society of Gene Therapy2025

Engineering resilient CAR T cells for immunosuppressive environment.

Malak Khalifeh, Huda Salman

Abstract readReview
In one paragraph

Review in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing 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

17 citing papers in PubMed.

  1. Review
  2. Article
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  13. From Bench to Bedside: Emerging Paradigms in CAR-T Cell Therapy for Solid Malignancies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  14. Review
  15. Review
  16. Medulloblastoma: biology and immunotherapy.Frontiers in immunology · 2025
    Review
  17. 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

2 authors.

Malak KhalifehBrown Center for Immunotherapy. IU Simon Comprehensive Cancer Center, Indiana University School of Medicine, 975 W. Walnut St., IB554A, Indianapolis, IN 46202, USA.
Huda SalmanBrown Center for Immunotherapy. IU Simon Comprehensive Cancer Center, Indiana University School of Medicine, 975 W. Walnut St., IB554A, Indianapolis, IN 46202, USA. Electronic address: hsalman@iu.edu.

Funding

Tumor Microenvironment and Metastasis ProgramP30CA082709 · NCI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI Sara K Quinney · 1999 to 2026
$59.3M
NCI NIH HHS P30 CA082709
6 · The paper itself

Abstract

Chimeric antigen receptor (CAR) T cell therapy has revolutionized cancer treatment and is now being explored for other diseases, such as autoimmune disorders. While the tumor microenvironment (TME) in cancer is often immunosuppressive, in autoimmune diseases, the environment is typically inflammatory. Both environments can negatively impact CAR T cell survival: the former through direct suppression, hypoxia, and nutrient deprivation, and the latter through chronic T cell receptor (TCR) engagement, risking exhaustion. Mechanisms of resistance include T cell exhaustion, dysfunction, and the impact of the TME. Chronic antigenic stimulation leads to CAR T cell exhaustion. CAR construct design, including co-stimulatory domains, hinge, transmembrane regions, promoters, the affinity of the binder site, and on/off rate plays a crucial role in modulating CAR T cell function and resistance. This review discusses the impact of the in vitro development of CAR T cells, albeit in relation to the TME, on therapeutic outcomes. The use of alternative cell sources, multi-antigen targeting, and reengineering the TME, are discussed. The review emphasizes the need for continued innovation in CAR T cell design and manufacturing to optimize therapeutic efficacy and durability, especially in the face of varying environmental challenges.

Indexed as

Immunotherapy, AdoptiveNeoplasmsReceptors, Antigen, T-CellReceptors, Chimeric AntigenT-LymphocytesAnimalsHumansTumor MicroenvironmentReceptors, Antigen, T-CellReceptors, Chimeric Antigenchimeric antigen receptor T therapyefficacyexhaustioninhibitory receptorspersistenceresistancetranscription factors

Identifiers

PMID39863931
PMCPMC12172186

What OpenQuestion holds

Textmetadata
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.