ArticleNature cancer2025
Engineering T cells with a membrane-tethered version of SLP-76 overcomes antigen-low resistance to CAR T cell therapy.
Article in Nature cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 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
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.
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Who cites it
6 citing papers in PubMed.
- A guide to CAR T cell therapies: development, current status and future prospects.Nature reviews. Immunology · 2026Review
- 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
- Recapitulating the qualities of HIV-specific CD8 + T cells from spontaneous controllers.Current opinion in HIV and AIDS · 2026Review
- 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
- CAR-T cell signaling dynamics, rational design principles and artificial intelligence for next-generation chimeric antigen receptors.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
20 authors.
Funding
Abstract
Chimeric antigen receptor (CAR) T cells can mediate durable complete responses in individuals with certain hematologic malignancies, but antigen downregulation is a common mechanism of resistance. Although the native T cell receptor can respond to very low levels of antigen, engineered CARs cannot, likely due to inefficient recruitment of downstream proximal signaling molecules. We developed a platform that endows CAR T cells with the ability to kill antigen-low cancer cells consisting of a membrane-tethered version of the cytosolic signaling adaptor molecule SLP-76 (MT-SLP-76). MT-SLP-76 can be expressed alongside any CAR to lower its activation threshold, overcoming antigen-low escape in multiple xenograft models. Mechanistically, MT-SLP-76 amplifies CAR signaling through recruitment of ITK and PLCγ1. MT-SLP-76 was designed based on biologic principles to render CAR T cell therapies less susceptible to antigen downregulation and is poised for clinical development to overcome this common mechanism of resistance.
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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.