The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Precision Tumor Recognition by T Cells With Combinatorial Antigen-Sensing Circuits
Open accessAbstract
SUMMARY T cells can be re-directed to kill cancer cells using chimeric antigen receptors (CARs) or T cell receptors (TCRs). This approach, however, is constrained by the rarity of tumor-specific single antigens. Targeting antigens also found on bystander tissues can cause life-threatening adverse effects. A powerful way to enhance ON-target activity of therapeutic T cells is to engineer them to require combinatorial antigens. Here we engineer a combinatorially activated T cell circuit in which a synthetic Notch receptor for one antigen induces the expression of a CAR for a second antigen. These dual receptor AND-gate T cells are only armed and activated in the presence of dual antigen tumor cells. These T cells show precise therapeutic discrimination in vivo – sparing single antigen “bystander” tumors while efficiently clearing combinatorial antigen “disease” tumors. This type of precision dual receptor circuit opens the door to immune recognition of a wider range of tumors.
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Citations
Cites
Chimeric antigen receptor–modified T cells in chronic lymphoid leukemia
Porter, D. L., Levine, B. L., Kalos, M., Bagg, A., & June, C. H. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1103849 · Cited by 3,565
Chimeric Antigen Receptor–Modified T Cells for Acute Lymphoid Leukemia
Grupp, S. A., Kalos, M., Barrett, D., Aplenc, R., Porter, D. L., Rheingold, S. R., Teachey, D. T., Chew, A., Hauck, B., Wright, J. F., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1215134 · Cited by 3,509
Molecular mechanisms of T cell co-stimulation and co-inhibition
Chen, L., & Flies, D. B. (2013) · Nature Reviews Immunology · doi:10.1038/nri3405 · Cited by 3,114
Brentjens, R. J., Davila, M. L., Riviere, I., Park, J., Wang, X., Cowell, L. G., Bartido, S., Stefanski, J., Taylor, C., Olszewska, M., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005930 · Cited by 2,063
Self-citation
Cited by
Car t cell immunotherapy for human cancer
June, C. H., O’Connor, R. S., Kawalekar, O. U., Ghassemi, S., & Milone, M. C. (2018) · Science · doi:10.1126/science.aar6711 · Cited by 3,207
Cytotoxic CD8+ T cells in cancer and cancer immunotherapy
Raskov, H., Orhan, A., Christensen, J. P., & Gögenur, I. (2021) · British Journal of Cancer · doi:10.1038/s41416-020-01048-4 · Cited by 1,687
Notch signaling pathway: architecture, disease, and therapeutics
Zhou, B., Lin, W., Long, Y., Yang, Y., Zhang, H., Wu, K., & Chu, Q. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00934-y · Cited by 1,114
The Principles of Engineering Immune Cells to Treat Cancer
Lim, W. A., & June, C. H. (2017) · Cell · doi:10.1016/j.cell.2017.01.016 · Cited by 1,080
Self-citationCancer stem cells—Origins and biomarkers: Perspectives for targeted personalized therapies
Walcher, L., Kistenmacher, A.-K., Suo, H., Kitte, R., Dluczek, S., Strauß, A., Blaudszun, A.-R., Yevsa, T., Fricke, S., & Kossatz-Boehlert, U. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01280 · Cited by 1,007
Metadata
- Authors
- Roybal, K. T., Rupp, L. J., Morsut, L., Walker, W. J., McNally, K. A., Park, J. S., & Lim, W. A.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-02
- Volume
- 164
- Issue
- 4
- Pages
- 770-779
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2258336271
- Cited by
- 1,000
- References
- 4
- FWCI
- 47.90
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Roybal, K. T., Rupp, L. J., Morsut, L., Walker, W. J., McNally, K. A., Park, J. S., & Lim, W. A. (2016). Precision Tumor Recognition by T Cells With Combinatorial Antigen-Sensing Circuits. Cell. https://doi.org/10.1016/j.cell.2016.01.011
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