| Autor: |
Sameeha Jilani, Justin D. Saco, Edurne Mugarza, Aleida Pujol-Morcillo, Jeffrey Chokry, Clement Ng, Gabriel Abril-Rodriguez, David Berger-Manerio, Ami Pant, Jane Hu, Rubi Gupta, Agustin Vega-Crespo, Ignacio Baselga-Carretero, Jia M. Chen, Daniel Sanghoon Shin, Philip Scumpia, Roxana A. Radu, Yvonne Chen, Antoni Ribas, Cristina Puig-Saus |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 15, Iss 1, Pp 1-19 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-024-45221-2 |
| Popis: |
Abstract A major limitation to developing chimeric antigen receptor (CAR)-T cell therapies for solid tumors is identifying surface proteins highly expressed in tumors but not in normal tissues. Here, we identify Tyrosinase Related Protein 1 (TYRP1) as a CAR-T cell therapy target to treat patients with cutaneous and rare melanoma subtypes unresponsive to immune checkpoint blockade. TYRP1 is primarily located intracellularly in the melanosomes, with a small fraction being trafficked to the cell surface via vesicular transport. We develop a highly sensitive CAR-T cell therapy that detects surface TYRP1 in tumor cells with high TYRP1 overexpression and presents antitumor activity in vitro and in vivo in murine and patient-derived cutaneous, acral and uveal melanoma models. Furthermore, no systemic or off-tumor severe toxicities are observed in an immunocompetent murine model. The efficacy and safety profile of the TYRP1 CAR-T cell therapy supports the ongoing preparation of a phase I clinical trial. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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