ArticleScience signaling2019
An immunoproteomic approach to characterize the CAR interactome and signalosome.
Article in Science signaling, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
What it found
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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
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Who cites it
99 citing papers in PubMed.
- CAR signaling instructs divergent metabolic reprogramming and functional fates in αβ and γδ T cells.Cellular & molecular immunology · 2026Article
- Short-chain fatty acids act as metabolic and epigenetic regulators in CAR T cell therapy.Molecular therapy. Oncology · 2026Review
- C-terminal CD28 phosphorylation, pY218, modulates IL-2 secretion and therapeutic effect of CAR-T cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Review
- High-Precision Intrinsic Interactome Elucidation of Chimeric Antigen Receptors via Photocatalytic Micromapping (μMap-CAR).Journal of the American Chemical Society · 2026Article
- Metabolic and functional analysis including repetitive antigen stimulation provides a more accurate assessment for CAR-T cell product quality and long-term functionality.Journal of translational medicine · 2026Article
- FcεRγI promotes canine CD8 chimeric antigen receptor T cell cytotoxicity through a Syk-NF-κB axis.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- C-terminus CD28 phosphorylation (Y218) modulates IL-2 secretion and antitumor effect of CAR-T cells.bioRxiv : the preprint server for biology · 2026Article
- Decoding signaling architectures: CAR versus TCR dynamics in solid tumor immunotherapy.Acta biochimica et biophysica Sinica · 2026Review
- CAR-engineered cell therapies: current understandings and future perspectives.Molecular biomedicine · 2026Review
- Adoptive T Cell therapy for cancer and autoimmune disease: current advances, challenges, and future directions.Oncology reviews · 2026Article
- Enhancing immunotherapy efficacy in multiple myeloma and chronic lymphocytic leukemia: from combinatorial therapeutic approaches to gut microbiota modulation.Frontiers in immunology · 2026Review
- CAR Cell-Derived Exosomes in Cancer Therapy: Biogenesis, Engineering Strategies and Antitumor Mechanisms.International journal of molecular sciences · 2025Review
- CD2 augmentation enhances CAR-T-cell efficacy via immunological synapse remodeling and T-cell exhaustion mitigation.Cellular & molecular immunology · 2025Article
- A Proteomics Outlook on the Molecular Effectors of CAR-T Cell Therapy in Cancer Management.Journal of proteome research · 2025Review
- A Checkpoint Reversal Receptor Mediates Bipartite Activation and Enhances CAR T-cell Function.Cancer research communications · 2025Article
- Advances in engineered T cell immunotherapy for autoimmune and other non-oncological diseases.Biomarker research · 2025Review
- From ex vivo to in vivo chimeric antigen T cells manufacturing: new horizons for CAR T-cell based therapy.Journal of translational medicine · 2025Review
- Metabolic reprogramming of CAR T cells: a new frontier in cancer immunotherapy.Frontiers in immunology · 2025Review
- Research progress on HER2-specific chimeric antigen receptor T cells for immunotherapy of solid tumors.Frontiers in immunology · 2025Review
39 more citing papers are in PubMed but not listed here.
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
Abstract
Adoptive transfer of T cells that express a chimeric antigen receptor (CAR) is an approved immunotherapy that may be curative for some hematological cancers. To better understand the therapeutic mechanism of action, we systematically analyzed CAR signaling in human primary T cells by mass spectrometry. When we compared the interactomes and the signaling pathways activated by distinct CAR-T cells that shared the same antigen-binding domain but differed in their intracellular domains and their in vivo antitumor efficacy, we found that only second-generation CARs induced the expression of a constitutively phosphorylated form of CD3ζ that resembled the endogenous species. This phenomenon was independent of the choice of costimulatory domains, or the hinge/transmembrane region. Rather, it was dependent on the size of the intracellular domains. Moreover, the second-generation design was also associated with stronger phosphorylation of downstream secondary messengers, as evidenced by global phosphoproteome analysis. These results suggest that second-generation CARs can activate additional sources of CD3ζ signaling, and this may contribute to more intense signaling and superior antitumor efficacy that they display compared to third-generation CARs. Moreover, our results provide a deeper understanding of how CARs interact physically and/or functionally with endogenous T cell molecules, which will inform the development of novel optimized immune receptors.
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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.