ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025
Asparaginase enhances CAR-T cell antitumor immunity by asparagine metabolic reprogramming and central memory induction in ALL.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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
5 citing papers in PubMed.
- Fusion Protein Technology to Enhance Pharmacological Properties of L-Asparaginases.Biomolecules · 2026Review
- In vivo CAR-T therapy: from molecular design to precision delivery.Journal of nanobiotechnology · 2026Review
- Silk protein plastics for sustained and controlled drug release.International journal of pharmaceutics · 2026Article
- Advances in CAR-T therapy for central nervous system lymphoma.Frontiers in immunology · 2026Review
- Suppression of ASNS expression by VHL-mediated ubiquitination hinders the progression of renal cell carcinoma through enhancing JUP expression and inhibiting PI3K-AKT and MAPK pathways.International journal of biological sciences · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High levels of asparagine synthetase (ASNS) in acute lymphoblastic leukemia (ALL) lead to immunotherapy resistance. Our study showed that ASNS overexpression (OE) in NALM6-GL cancer cells attenuated chimeric antigen receptor (CAR)-T cell-mediated cancer cell lysis. Asparaginase (ASPG) is an approved drug that breaks down circulating asparagine in leukemia cells, thereby depriving cancer cells of asparagine and inhibiting cancer growth. We proposed a hypothesis that ASPG-engineered CAR-T cells undergo phenotype switching to overcome immunotherapy resistance in ALL. Coculture killing assay showed ASPG-OE CAR-T cells exhibited increased killing efficacy against ASNS-OE cancer cells by enhancing the expression of granzyme B, interferon gamma, and tumor necrosis factor alpha, whereas ASPG-knockout (KO) CAR-T cells showed decreased cancer cell lysis efficiency. Phenotypic analysis revealed that ASPG-OE CAR-T cells exhibited distinct phenotypes, including increasing central memory T cells percentage, while decreasing effector memory T cells and effector memory cells that re-expressed CD45RA cells proportions. This distinct phenotype switch of ASPG-OE CAR-T cells toward central memory T cells exerted the increased killing efficacy against NALM6-GL cells even without ASNS-OE. The in vivo xenograft mouse model confirmed that ASPG-OE CAR-T cells exhibited superior anticancer activity against NALM6-GL cancer cells, while ASPG-KO CAR-T cells exhibited inferior anticancer activity. Taken together, ASPG orchestrates CAR-T cell distinct phenotype toward central memory T cells and reprogramming of asparagine metabolism for enhancing antitumor immunity.
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.