ArticleGenes & genomics2026
Synergistic antitumor activity of CAR-NK cells combined with CAR-macrophages for pancreatic cancer treatment.
Article in Genes & genomics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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.
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.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
backgroundAdoptive cell therapies employing chimeric antigen receptors (CARs) have achieved remarkable success in hematologic malignancies, yet their efficacy in solid tumors remains limited due to the immunosuppressive tumor microenvironment (TME), which restricts immune cell infiltration and persistence. While CAR-NK cells provide potent cytotoxicity with a favorable safety profile, their tumor penetration is often suboptimal. In contrast, macrophages possess intrinsic tumor-homing and tissue-remodeling abilities that could help overcome these barriers.
objectiveThis study aimed to develop a combinatorial innate-cell immunotherapy integrating nanobody-based mesothelin (MSLN)-targeting CAR-macrophages (CAR-Ms) with CAR-NK cells to remodel the TME and enhance antitumor immunity in pancreatic cancer.
methodsUsing a validated D3 nanobody CAR construct, CAR-Ms were generated from PMA-differentiated THP-1 monocytes and characterized for CAR expression, M1/M2 polarization, migration, phagocytosis, and cytokine secretion. CAR-NK cell migration and cytotoxicity were evaluated using conditioned media (CM) from CAR-M/tumor co-cultures. Synergistic antitumor activity was assessed in an orthotopic MSLN⁺ pancreatic ductal adenocarcinoma (PDAC) model.
resultsD3-CAR-Ms exhibited robust CAR expression (> 90%) and sustained an M1-like phenotype (CD86⁺HLA-DR⁺CD204⁻) even after tumor engagement. Functionally, they displayed enhanced migration and infiltration into MSLN⁺ PANC-1 spheroids, along with increased phagocytic and tumoricidal activity. Upon antigen engagement, CAR-Ms secreted high levels of CXCL9, which promoted CAR-NK chemotaxis, degranulation, and cytotoxicity. Sequential administration of CAR-Ms and CAR-NK cells in vivo led to marked tumor regression and durable responses without systemic toxicity.
conclusionCombinatorial nanobody-based CAR-M and CAR-NK therapy reprograms the TME and establishes a CXCL9-driven feed-forward loop between macrophages and NK cells, leading to synergistic innate immune activation and potent tumor control. This strategy provides a mechanistically grounded and translationally feasible framework for next-generation CAR-based immunotherapies targeting MSLN-expressing solid tumors.
Indexed as
Identifiers
41627624What OpenQuestion holds
Registered trials
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.