Evidence map›Paper›PMID 39617146›Full record

ReviewPharmacology & therapeutics2025

Combinational CAR T-cell therapy for solid tumors: Requisites, rationales, and trials.

Kyohei Misawa, Hina Bhat, Prasad S Adusumilli, Zhaohua Hou

Abstract readReview
In one paragraph

Review in Pharmacology & therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing 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

18 citing papers in PubMed.

  1. Review
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  3. Irreversible Electroporation Enhances Solid Tumor Infiltration and Selective Cancer Cell Lysis by CAR T Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Article
  4. Advances in targeted and cellular therapies for relapsed/refractory mantle cell lymphoma: immunotherapeutic strategies and challenges.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
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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

4 authors.

Kyohei MisawaThoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Hina BhatThoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. Electronic address: adusumip@mskcc.org.
Prasad S AdusumilliThoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA; Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. Electronic address: adusumip@mskcc.org.
Zhaohua HouThoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
SURGICAL ONCOLOGY RESEARCH TRAINING PROGRAMT32CA009501 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Babak J Mehrara · 1985 to 2026
$7.7M
A phase I/II combination immunotherapy clinical trial: mesothelin-targeted chimeric antigen receptor T cells and checkpoint blockade agent in pleural mesotheliomaR01CA235667 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI ADUSUMILLI, PRASAD S. · 2019 to 2024
$3.6M
The EDRN Mesothelioma Biomarker Discovery LaboratoryU01CA214195 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI PASS, HARVEY IRA, YANG, HAINING · 2016 to 2021
$3.5M
Tuning KITv CAR T cells for the solid tumor environmentR01CA292664 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Prasad S. Adusumilli · 2024 to 2026
$3.2M
CD28-KITv CAR T cells with PD-1 dominant negative receptorUG3CA290241 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI ADUSUMILLI, PRASAD S. · 2024 to 2025
$3.1M
Image-guided irreversible electroporation directed CAR T-cell delivery to solid tumorsR01CA236615 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI ADUSUMILLI, PRASAD S., SOLOMON, STEPHEN BARNETT · 2018 to 2022
$2.0M
Mitochondrial Mutagenesis and Dysfunction in Cancer MetabolismF30CA200247 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI VALENTE, WILLIAM JOSEPH · 2015 to 2017
$130k
NCI NIH HHS F30 CA200247NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA235667NCI NIH HHS R01 CA236615NCI NIH HHS R01 CA292664NCI NIH HHS T32 CA009501NCI NIH HHS U01 CA214195NCI NIH HHS UG3 CA290241
6 · The paper itself

Abstract

Chimeric antigen receptor (CAR) T-cell therapy has achieved potent antitumor efficacy in hematological malignancies; however, because of limitations in CAR T-cell recruitment, infiltration, activation, and functional persistence in the tumor, its efficacy in solid tumors has been suboptimal. To overcome these challenges, combinational strategies that include chemotherapy, radiation therapy, or immune checkpoint inhibitor agent therapy with CAR T-cell therapy are being investigated. The established functional characteristics of the abovementioned therapies provide a rationale for the use of a combinational approach with CAR T cells. Chemotherapy reshapes the peritumoral stroma, decreases the immunosuppressive cell population, and promotes a proinflammatory milieu, all of which allow for increased recruitment, infiltration, and accumulation of CAR T cells. Radiation therapy promotes a chemokine gradient, which augments tumor infiltration by CAR T cells and further increases expression of tumor-associated antigens, allowing for increased activation of CAR T cells. Immune checkpoint inhibitor agent therapy inactivates T-cell exhaustion pathways-most notably, the PD1/PDL1 pathway-thereby improving the functional persistence of CAR T cells and promoting endogenous immunity. In this review, we discuss the requisites and rationales for combinational therapy, and we review 25 ongoing phase I and II clinical trials, of which 4 use chemotherapy, 3 use radiation therapy, 11 use immunotherapy, and 7 use another agent. While safety, efficacy, and improved outcomes are the primary goals of these ongoing studies, the knowledge gained from them will help pave the way for subsequent studies focused on optimizing combinational regimens and identifying predictive biomarkers.

Indexed as

Immunotherapy, AdoptiveNeoplasmsReceptors, Chimeric AntigenAnimalsClinical Trials as TopicCombined Modality TherapyHumansImmune Checkpoint InhibitorsT-LymphocytesImmune Checkpoint InhibitorsReceptors, Chimeric AntigenCAR T cellsCheckpoint blockadeChemotherapyCombinational therapyImmunotherapyRadiation therapyRegional delivery

Identifiers

PMID39617146
PMCPMC11848936

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.