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| Item Type: | Article |
|---|---|
| Title: | TCR/CD3-based synthetic antigen receptors (TCC) convey superior antigen sensitivity combined with high fidelity of activation |
| Creators Name: | Mühlgrabner, V., Peters, T., Velasco Cárdenas, R.M.H., Salzer, B., Göhring, J., Plach, A., Höhrhan, M., Perez, I.D., Goncalves, V.D.R., Farfán, J.S., Lehner, M., Stockinger, H., Schamel, W.W., Schober, K., Busch, D.H., Hudecek, M., Dushek, O., Minguet, S., Platzer, R. and Huppa, J.B. |
| Abstract: | Low antigen sensitivity and a gradual loss of effector functions limit the clinical applicability of chimeric antigen receptor (CAR)–modified T cells and call for alternative antigen receptor designs for effective T cell–based cancer immunotherapy. Here, we applied advanced microscopy to demonstrate that TCR/CD3-based synthetic constructs (TCC) outperform second-generation CAR formats with regard to conveyed antigen sensitivities by up to a thousandfold. TCC-based antigen recognition occurred without adverse nonspecific signaling, which is typically observed in CAR–T cells, and did not depend—unlike sensitized peptide/MHC detection by conventional T cells—on CD4 or CD8 coreceptor engagement. TCC-endowed signaling properties may prove critical when targeting antigens in low abundance and aiming for a durable anticancer response. |
| Keywords: | Adoptive Immunotherapy, CD3 Complex, Chimeric Antigen Receptors, Lymphocyte Activation, Signal Transduction, T-Cell Antigen Receptors, T-Lymphocytes, Tumor Cell Line |
| Source: | Science Advances |
| ISSN: | 2375-2548 |
| Publisher: | American Association for the Advancement of Science |
| Volume: | 10 |
| Number: | 36 |
| Page Range: | eadj4632 |
| Date: | 6 September 2024 |
| Official Publication: | https://doi.org/10.1126/sciadv.adj4632 |
| PubMed: | View item in PubMed |
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