ArticleHepatology communications2026
Manufacturing and electrostatic surface optimization of CAR-T cells improve therapeutic efficacy in liver malignancies.
Article in Hepatology communications, 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
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChimeric antigen receptor T-cell (CAR-T) therapy has achieved remarkable success in hematologic malignancies, yet demonstrates limited efficacy in solid tumors, including hepatic cancers. T-cell exhaustion and insufficient persistence represent major obstacles. We hypothesized that optimizing both manufacturing processes and CAR structural design could reduce exhaustion and enhance therapeutic outcomes in immunocompetent mouse models of primary and metastatic liver malignancies.
methodsWe systematically compared antibody-based versus bead-based activation methods, evaluating their effects on T-cell exhaustion phenotypes. Retroviral vector (RVV) production was optimized for murine T-cell transduction, assessing vector stability and T-cell phenotypes. Different cytokine conditions were tested for their impact on T-cell expansion, memory phenotypes, and anti-tumor efficacy using GPC3-targeted CAR-T cells in hepatocellular carcinoma models. Through structural prediction and electrostatic field simulation, we identified that high positive charge patches (PCP) in the EpCAM-targeting G8.8 scFv caused CAR clustering and tonic signaling. We generated charge-optimized variants and evaluated their therapeutic efficacy in an immunocompetent colorectal cancer liver metastasis model.
resultsAntibody activation showed superior homogeneity and expansion despite initially higher exhaustion markers, which equilibrated by day 10 without affecting viability. RVV harvested at 72 hours post-transfection yielded optimal titers. RVV remained stable through freeze-thaw cycles. IL-7 supplementation to IL-2 significantly enhanced memory phenotypes, reduced exhaustion, and improved tumor control in GPC3-CAR-T therapy. Electrostatic optimization of G8.8 scFv substantially reduced tonic signaling, decreased T-cell exhaustion, and enhanced anti-tumor efficacy in the MC38-EpCAM model.
conclusionsSystematic optimization of manufacturing conditions and structure-based charge engineering of CAR constructs synergistically enhance therapeutic efficacy against liver malignancies, providing a translatable framework for improving solid tumor CAR-T therapy.
Indexed as
Identifiers
What 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.