ArticleCancer cell2025
Restoration of LAT activity improves CAR T cell sensitivity and persistence in response to antigen-low acute lymphoblastic leukemia.
Article in Cancer cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed.
- FOXP1 Knockdown Reprograms Th9 CAR-T Cells to Overcome Antigen Escape.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- FATP2-mediated lipid metabolism enhances chimeric antigen receptor T-cell therapy resistance in B-cell acute lymphoblastic leukemia.Leukemia · 2026Article
- Mechanisms, optimization strategies, and salvage options for CAR-T cell therapy.Biomarker research · 2026Review
- A guide to CAR T cell therapies: development, current status and future prospects.Nature reviews. Immunology · 2026Review
- Humanized biparatopic nanobody-based CAR-T cells overcome antigen-heterogeneity in multiple myeloma.Journal of translational medicine · 2026Article
- Chimeric switch scaffold protein augments CAR synapse formation and signaling networks.Journal for immunotherapy of cancer · 2026Article
- Enhancing persistence while managing cytokine release syndrome to embrace next-generation CAR-T cell therapy.Journal of translational medicine · 2026Review
- Challenges and advances in CAR-T cell therapy for B-ALL.Biomarker research · 2026Review
- Rational redesign of antigen binding domain improves in vivo efficacy of the CD22-CAR.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- CD147 regulates CD8iScience · 2026Article
- The race between 4-1BB- and CD28-based CD19 CAR-T products in the therapy of B-cell malignancies.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- Decoding signaling architectures: CAR versus TCR dynamics in solid tumor immunotherapy.Acta biochimica et biophysica Sinica · 2026Review
- Next-generation CAR-T cells design: leveraging tumor features for enhanced efficacy.Molecular cancer · 2025Review
- Engineering T cells with a membrane-tethered version of SLP-76 overcomes antigen-low resistance to CAR T cell therapy.Nature cancer · 2025Article
- Increased NFAT activity with dual CAR stimulation in CD19xCD22 CAR T-cells is associated with decreased exhaustion and improved survival.Journal for immunotherapy of cancer · 2025Article
- Pioneering biomimetic biomaterial for leukemia therapy enhancement: a review.Frontiers in bioengineering and biotechnology · 2025Review
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
Chimeric antigen receptor (CAR) T cells induce responses in patients with relapsed/refractory leukemia; however, long-term efficacy is frequently limited by relapse. The inability to target antigen-low cells is an intrinsic vulnerability of second-generation CAR T cells and underlies most relapses following CD22BBz CAR T cell therapy. Here, we interrogate CD22BBz CAR signaling in response to low antigen and find inefficient phosphorylation of the linker for activation of T cells (LAT) limiting downstream signaling. To overcome this, we designed the adjunctive LAT-activating CAR T cell (ALA-CART) platform, pairing a second-generation CAR with a LAT-CAR incorporating the intracellular domain of LAT. ALA-CART cells demonstrate reduced differentiation during manufacturing and increased LAT phosphorylation, MAPK signaling, and AP-1 activity. ALA-CART cells show improved cytotoxicity, proliferation, persistence, and efficacy against antigen-low leukemias that were refractory to clinically active CD22BBz CAR T cells. Restoration of LAT signaling through the ALA-CART platform represents a promising strategy for overcoming multiple mechanisms of CAR T cell failure.
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.