ArticleProceedings of the National Academy of Sciences of the United States of America2024
Engineered CD4 T cells for in vivo delivery of therapeutic proteins.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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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
8 citing papers in PubMed.
- The proteomics and phosphoproteomics landscape of melanoma under T cell attack.Cell reports. Medicine · 2026Article
- Cell-Derived Nanocarriers for Monocyte-Mediated Therapeutic Delivery: Concept and Challenges.Yonsei medical journal · 2026Review
- Establishing an RNA Sensor with High Sensitivity and Dynamic Range Utilizing a Signal Amplifier Platform.ACS synthetic biology · 2026Article
- CD4 T-cell platform for delivering interferons as an antiviral countermeasure with a focus on SARS-CoV-2.Molecular medicine (Cambridge, Mass.) · 2026Article
- Immunocyte reprogramming empowers live-cell drug delivery: Mechanistic insights, delivery strategies, and clinical perspectives.Acta pharmaceutica Sinica. B · 2026Review
- Smart Cells Against Cancer: Advances in Cell-Based Drug Delivery and Diagnostics.Pharmaceutics · 2025Review
- Syngeneic CAR T cells engineered for persistent delivery of desired proteins.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- Establishing an RNA sensor with high sensitivity and dynamic range utilizing a signal amplifier platform.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
The CD4 T cell, when engineered with a chimeric antigen receptor (CAR) containing specific intracellular domains, has been transformed into a zero-order drug-delivery platform. This introduces the capability of prolonged, disease-specific engineered protein biologics production, at the disease site. Experimental findings demonstrate that CD4 T cells offer a solution when modified with a CAR that includes 4-1BB but excludes CD28 intracellular domain. In this configuration, they achieve ~3X transduction efficiency of CD8 T cells, ~2X expansion rates, generating ~5X more biologic, and exhibit minimal cytolytic activity. Cumulatively, this addresses two main hurdles in the translation of cell-based drug delivery: scaling the production of engineered T cell ex vivo and generating sufficient biologics in vivo. When programmed to induce IFNβ upon engaging the target antigen, the CD4 T cells outperforms CD8 T cells, effectively suppressing cancer cell growth in vitro and in vivo. In summary, this platform enables precise targeting of disease sites with engineered protein-based therapeutics while minimizing healthy tissue exposure. Leveraging CD4 T cells' persistence could enhance disease management by reducing drug administration frequency, addressing critical challenges in cell-based therapy.
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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.