Evidence map›Paper›PMID 40981226›Full record

ReviewMethods and protocols2025

Mechanisms of Resistance to CAR T-Cells and How to Overcome Them.

Luca Legato, Matteo Bisio, Filippo Fasano, Corrado Benevolo Savelli, Carolina Secreto, Chiara Maria Dellacasa, Barbara Botto, Alessandro Busca, Marco Cerrano, Roberto Freilone and 1 more

Abstract readReview
In one paragraph

Review in Methods and protocols, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
  2. In Vivo CAR-T Therapies-A New Era of Programmable Immunity.International journal of molecular sciences · 2026
    Review
  3. Article
  4. Review
  5. Review
  6. 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

11 authors.

Luca LegatoDivision of Hematology and Allogeneic Stem Cell Transplant Unit, A.O.U. Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy.
Matteo BisioDivision of Hematology and Allogeneic Stem Cell Transplant Unit, A.O.U. Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy.
Filippo FasanoDivision of Hematology and Allogeneic Stem Cell Transplant Unit, A.O.U. Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy.ORCID 0009-0001-5591-2686
Corrado Benevolo SavelliDivision of Hematology and Allogeneic Stem Cell Transplant Unit, A.O.U. Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy.
Carolina SecretoDivision of Hematology and Allogeneic Stem Cell Transplant Unit, A.O.U. Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy.
Chiara Maria DellacasaDivision of Hematology and Allogeneic Stem Cell Transplant Unit, A.O.U. Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy.
Barbara BottoDivision of Hematology and Allogeneic Stem Cell Transplant Unit, A.O.U. Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy.ORCID 0009-0005-7514-6172
Alessandro BuscaDivision of Hematology and Allogeneic Stem Cell Transplant Unit, A.O.U. Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy.ORCID 0000-0001-5361-5613
Marco CerranoDivision of Hematology and Allogeneic Stem Cell Transplant Unit, A.O.U. Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy.
Roberto FreiloneDivision of Hematology and Allogeneic Stem Cell Transplant Unit, A.O.U. Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy.ORCID 0000-0002-6003-3328
Mattia NovoDivision of Hematology and Allogeneic Stem Cell Transplant Unit, A.O.U. Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy.ORCID 0000-0002-5127-3653

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In the last few decades, chimeric antigen receptor (CAR) T-cell therapy has led to a paradigm shift in the treatment of hematological malignancies, including various subtypes of B-cell non-Hodgkin's lymphoma, B-cell acute lymphoblastic leukemia, and multiple myeloma. However, most patients experience refractoriness to CAR T-cells or relapse after treatment. Many efforts are underway to understand the mechanisms behind CAR T-cell failure, which are mainly related to CAR T-cell dysfunction, tumor-intrinsic resistance, an immunosuppressive tumor microenvironment, manufacturing issues, or patient-related factors. Several strategies are being developed to overcome these resistance mechanisms, including the engineering of more functional allogeneic CAR T-cell products, the targeting of alternative tumor antigens, and combination therapies with other drugs such as checkpoint inhibitors or small molecules to enhance CAR T-cell efficacy. In this review, we will provide an updated overview of the mechanisms of CAR T-cell failure and the therapeutic advances currently under development to address them.

Indexed as

allogeneic CAR T-cellsB-cell acute lymphoblastic leukemiaB-cell lymphomaCAR NKCAR T-cell resistanceCAR T-cellsdual targetingmultiple myeloma

Identifiers

PMID40981226
PMCPMC12452515

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.