ArticleThe Journal of experimental medicine2024
PROTAC-mediated NR4A1 degradation as a novel strategy for cancer immunotherapy.
Article in The Journal of experimental medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Single-cell and spatial transcriptomic profiling reveals distinct immune landscapes in murine lungs infected with H1N1 versus H5N1 influenza viruses.Journal of virology · 2026Article
- MerTK Is Regulated by Orphan Nuclear Receptor 4A1 (NR4A1) and NR4A2 in Colon Cancer Cells.Cancers · 2026Article
- Decoding the crosstalk between ubiquitination and other post-translational modifications in cancer immunity: from mechanisms to clinical prospects.NPJ precision oncology · 2026Review
- A lipid nanoparticle-based peptide-proteolysis-targeting chimera degrades BCL6 for diffuse large B-cell lymphoma treatment.Discover oncology · 2026Article
- Precision immunotherapy for head and neck cancer: therapeutic combinations, biomarker strategies, and translational challenges.Molecular cancer · 2026Review
- PROTAC-based protein degradation: a window of opportunity for melanoma therapy.Journal of biomedical science · 2026Review
- Reversible control of T cell exhaustion by NR4A transcription factors revealed through targeted protein degradation.bioRxiv : the preprint server for biology · 2026Article
- Regulators of CD8Nature reviews. Immunology · 2026Review
- Regulation of T cell exhaustion and stemness: molecular mechanisms and implications for cancer immunotherapy.Cellular & molecular immunology · 2026Review
- NR4A nuclear receptor expression in human macrophages mediates apoptosis and controls Mycobacterium tuberculosis growth.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Targeting Lineage-Specific Functions of NR4A1 for Cancer Immunotherapy.International journal of molecular sciences · 2025Review
- Targeting the nuclear orphan receptor NR4A1: a key target in lung cancer progression and therapeutic resistance.Frontiers in oncology · 2025Review
- PTGES3 proteolysis using the liposomal peptide-PROTAC approach.Biology direct · 2024Article
- Targeted Protein Degradation (TPD) for Immunotherapy: Understanding Proteolysis Targeting Chimera-Driven Ubiquitin-Proteasome Interactions.Bioconjugate chemistry · 2024Review
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22 authors at 6 institutions in 2 countries.
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Abstract
An effective cancer therapy requires killing cancer cells and targeting the tumor microenvironment (TME). Searching for molecules critical for multiple cell types in the TME, we identified NR4A1 as one such molecule that can maintain the immune suppressive TME. Here, we establish NR4A1 as a valid target for cancer immunotherapy and describe a first-of-its-kind proteolysis-targeting chimera (PROTAC, named NR-V04) against NR4A1. NR-V04 degrades NR4A1 within hours in vitro and exhibits long-lasting NR4A1 degradation in tumors with an excellent safety profile. NR-V04 inhibits and frequently eradicates established tumors. At the mechanistic level, NR-V04 induces the tumor-infiltrating (TI) B cells and effector memory CD8+ T (Tem) cells and reduces monocytic myeloid-derived suppressor cells (m-MDSC), all of which are known to be clinically relevant immune cell populations in human melanomas. Overall, NR-V04-mediated NR4A1 degradation holds promise for enhancing anticancer immune responses and offers a new avenue for treating various types of cancers such as melanoma.
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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.