Evidence map›Paper›PMID 41558599›Full record

ArticleJournal of advanced research2026

Distinct effector functions and synergy of CAR mRNA-engineered T cells and macrophages in the clearance of CD19

Liangliang Liao, Cheng Lin, Adrian Kuzmanović, Nan Wang, Alexander Jans, Christian Penners, Kim Ohl, Sandra Johnen, Reka Geczy, Martin Rabel and 4 more

Abstract read
In one paragraph

Article in Journal of advanced research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

14 authors.

Liangliang LiaoDepartment of Internal Medicine III, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; Department of Gastric Colorectal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China.
Cheng LinDepartment of Internal Medicine III, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; Department of Rheumatology and Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China.
Adrian KuzmanovićDepartment of Internal Medicine III, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, Germany.
Nan WangDepartment of Internal Medicine III, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Alexander JansDepartment of Internal Medicine III, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, Germany.
Christian PennersDepartment of Internal Medicine III, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, Germany.
Kim OhlDepartment of Pediatrics, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, Germany.
Sandra JohnenDepartment of Ophthalmology, RWTH Aachen University, Aachen, Germany.
Reka GeczyCytiva, 1055 Vernon Drive, Vancouver, BC V6A 3P4, Canada.
Martin RabelCytiva, 1055 Vernon Drive, Vancouver, BC V6A 3P4, Canada.
Samuel ClarkeCytiva, 1055 Vernon Drive, Vancouver, BC V6A 3P4, Canada.
Aruna BalgiCytiva, 1055 Vernon Drive, Vancouver, BC V6A 3P4, Canada.
Christian LiedtkeDepartment of Internal Medicine III, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, Germany.
Matthias BartneckDepartment of Internal Medicine III, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; DWI - Leibniz Institute for Interactive Materials, Forckenbeckstraße 50, 52074 Aachen, Germany; Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, Worringerweg 2, 52074 Aachen, Germany. Electronic address: mbartneck@ukaachen.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionChimeric antigen receptor (CAR) technology represents a groundbreaking advancement in gene therapy. While CAR-T cells are approved for specific types of leukemia, the therapeutic potential of CAR-macrophages remains largely unexplored. Additionally, potentially synergistic effects between CAR-T cells and CAR-macrophages in cancer cell clearance are still elusive.

objectivesThis study aimed to investigate the efficiency and mechanisms of human CAR-T cells and CAR-macrophages for clearing cancer cells using co-culture experiments.

methodsWe encapsulated a second generation CD19 CAR mRNA or enhanced green fluorescent protein (Egfp) encoding control mRNA into lipid nanoparticles (LNP) using different methods. We transfected human primary T cells or macrophages with these LNP and studied their CAR expression using flow cytometry or confocal microscopy. Killing and phagocytosis assays were conducted to evaluate the impact of CAR-T cells and CAR-macrophages on CD19

resultsActivated T cells upregulated the low-density lipoprotein receptor (LDLR), resulting in higher CAR surface expression post-transfection than in non-activated T cells. CAR-T cells efficiently induced death of lymphoma cells. CAR-macrophages cleared cancer cells mainly via phagocytosis and CAR mRNA altered the expression of both M1 and M2-associated genes. Interestingly, CAR macrophages also upregulated the Signal regulatory protein alpha (SIRPA), a receptor of the CD47 ligand expressed by cancer cells, and knockdown of SIRPA by siRNA efficiently counteracted this phenomenon. We noted a decrease in the motility of macrophages, T cells, and cancer cells in co-cultures containing CAR-transfected effector cells. Co-culturing CAR-T cells with CAR-macrophages synergistically enhanced tumor cell eradication.

conclusionOur findings underscore the superior cancer cell-killing capability of CAR-T cells. Additionally, CAR-macrophages play a crucial role in clearing cancer cells through phagocytosis, thereby synergistically supporting the activity of CAR-T cells.

Indexed as

Antigens, CD19Immunotherapy, AdoptiveLeukemiaMacrophagesReceptors, Chimeric AntigenRNA, MessengerT-LymphocytesCell Line, TumorCoculture TechniquesHumansPhagocytosisAntigens, CD19CD19 molecule, humanReceptors, Chimeric AntigenRNA, MessengerChimeric antigen receptorLive-cell imagingMotilitymRNAPhagocytosisSIRPA

Identifiers

PMID41558599
PMCPMC13669678

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.