TYRP1 directed CAR T cells control tumor progression in preclinical melanoma models
Despite therapeutic efficacy observed with immune checkpoint blockade in advanced melanoma, many tumors do not respond to treatment, representing a need for new therapies. Here, we have generated chimeric antigen receptor (CAR) T cells targeting TYRP1, a melanoma differentiation antigen expressed on...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-09-01
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| Series: | Molecular Therapy: Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950329924001048 |
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| author | Christopher S. Hackett Daniel Hirschhorn Meixian S. Tang Terence J. Purdon Yacine Marouf Alessandra Piersigilli Narasimhan P. Agaram Cailian Liu Sara E. Schad Elisa de Stanchina Sarwish Rafiq Sebastien Monette Jedd D. Wolchok Taha Merghoub Renier J. Brentjens |
| author_facet | Christopher S. Hackett Daniel Hirschhorn Meixian S. Tang Terence J. Purdon Yacine Marouf Alessandra Piersigilli Narasimhan P. Agaram Cailian Liu Sara E. Schad Elisa de Stanchina Sarwish Rafiq Sebastien Monette Jedd D. Wolchok Taha Merghoub Renier J. Brentjens |
| author_sort | Christopher S. Hackett |
| collection | DOAJ |
| description | Despite therapeutic efficacy observed with immune checkpoint blockade in advanced melanoma, many tumors do not respond to treatment, representing a need for new therapies. Here, we have generated chimeric antigen receptor (CAR) T cells targeting TYRP1, a melanoma differentiation antigen expressed on the surface of melanomas, including rare acral and uveal melanomas. TYRP1-targeted CAR T cells demonstrate antigen-specific activation and cytotoxic activity in vitro and in vivo against human melanomas independent of the MHC alleles and expression. In addition, the toxicity to pigmented normal tissues observed with T lymphocytes expressing TYRP1-targeted TCRs was not observed with TYRP1-targeted CAR T cells. Anti-TYRP1 CAR T cells provide a novel means to target advanced melanomas, serving as a platform for the development of similar novel therapeutic agents and as a tool to interrogate the immunobiology of melanomas. |
| format | Article |
| id | doaj-art-50d77f52a8984498bb99701a99596c2c |
| institution | Kabale University |
| issn | 2950-3299 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncology |
| spelling | doaj-art-50d77f52a8984498bb99701a99596c2c2024-11-24T04:15:47ZengElsevierMolecular Therapy: Oncology2950-32992024-09-01323200862TYRP1 directed CAR T cells control tumor progression in preclinical melanoma modelsChristopher S. Hackett0Daniel Hirschhorn1Meixian S. Tang2Terence J. Purdon3Yacine Marouf4Alessandra Piersigilli5Narasimhan P. Agaram6Cailian Liu7Sara E. Schad8Elisa de Stanchina9Sarwish Rafiq10Sebastien Monette11Jedd D. Wolchok12Taha Merghoub13Renier J. Brentjens14Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA; Swim Across America and Ludwig Collaborative Laboratory, Department of Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA; Parker Institute for Cancer Immunotherapy and Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, NY 10065, USASwim Across America and Ludwig Collaborative Laboratory, Department of Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA; Parker Institute for Cancer Immunotherapy and Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, NY 10065, USASwim Across America and Ludwig Collaborative Laboratory, Department of Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA; Parker Institute for Cancer Immunotherapy and Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, NY 10065, USARoswell Park Cancer Center, Buffalo, NY 14203, USASwim Across America and Ludwig Collaborative Laboratory, Department of Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA; Parker Institute for Cancer Immunotherapy and Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, NY 10065, USALaboratory of Comparative Pathology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, The Rockefeller University, New York, NY 10065, USADepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USASwim Across America and Ludwig Collaborative Laboratory, Department of Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA; Parker Institute for Cancer Immunotherapy and Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, NY 10065, USASwim Across America and Ludwig Collaborative Laboratory, Department of Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA; Parker Institute for Cancer Immunotherapy and Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, NY 10065, USAHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USADepartment of Hematology and Medical Oncology, Emory University School of Medicine, and Winship Cancer Institute, Atlanta, GA 30322, USALaboratory of Comparative Pathology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, The Rockefeller University, New York, NY 10065, USADepartment of Medicine, Weill Cornell Medicine, New York, NY 10065, USA; Swim Across America and Ludwig Collaborative Laboratory, Department of Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA; Parker Institute for Cancer Immunotherapy and Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, NY 10065, USA; Corresponding author: Jedd D. Wolchok, Department of Medicine, Swim Across America and Ludwig Collaborative Laboratory, Parker Institute for Cancer Immunotherapy and Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, NY 10065, USA.Swim Across America and Ludwig Collaborative Laboratory, Department of Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA; Parker Institute for Cancer Immunotherapy and Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, NY 10065, USA; Corresponding author: Taha Merghoub, Swim Across America and Ludwig Collaborative Laboratory, Department of Pharmacology, Parker Institute for Cancer Immunotherapy and Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, NY 10065, USA.Roswell Park Cancer Center, Buffalo, NY 14203, USA; Corresponding author: Renier J. Brentjens, Roswell Park Cancer Center, Buffalo, NY 14203, USA.Despite therapeutic efficacy observed with immune checkpoint blockade in advanced melanoma, many tumors do not respond to treatment, representing a need for new therapies. Here, we have generated chimeric antigen receptor (CAR) T cells targeting TYRP1, a melanoma differentiation antigen expressed on the surface of melanomas, including rare acral and uveal melanomas. TYRP1-targeted CAR T cells demonstrate antigen-specific activation and cytotoxic activity in vitro and in vivo against human melanomas independent of the MHC alleles and expression. In addition, the toxicity to pigmented normal tissues observed with T lymphocytes expressing TYRP1-targeted TCRs was not observed with TYRP1-targeted CAR T cells. Anti-TYRP1 CAR T cells provide a novel means to target advanced melanomas, serving as a platform for the development of similar novel therapeutic agents and as a tool to interrogate the immunobiology of melanomas.http://www.sciencedirect.com/science/article/pii/S2950329924001048MT: Regular Issuemelanomaacraluvealchimeric antigen receptoradoptive cellular therapy |
| spellingShingle | Christopher S. Hackett Daniel Hirschhorn Meixian S. Tang Terence J. Purdon Yacine Marouf Alessandra Piersigilli Narasimhan P. Agaram Cailian Liu Sara E. Schad Elisa de Stanchina Sarwish Rafiq Sebastien Monette Jedd D. Wolchok Taha Merghoub Renier J. Brentjens TYRP1 directed CAR T cells control tumor progression in preclinical melanoma models Molecular Therapy: Oncology MT: Regular Issue melanoma acral uveal chimeric antigen receptor adoptive cellular therapy |
| title | TYRP1 directed CAR T cells control tumor progression in preclinical melanoma models |
| title_full | TYRP1 directed CAR T cells control tumor progression in preclinical melanoma models |
| title_fullStr | TYRP1 directed CAR T cells control tumor progression in preclinical melanoma models |
| title_full_unstemmed | TYRP1 directed CAR T cells control tumor progression in preclinical melanoma models |
| title_short | TYRP1 directed CAR T cells control tumor progression in preclinical melanoma models |
| title_sort | tyrp1 directed car t cells control tumor progression in preclinical melanoma models |
| topic | MT: Regular Issue melanoma acral uveal chimeric antigen receptor adoptive cellular therapy |
| url | http://www.sciencedirect.com/science/article/pii/S2950329924001048 |
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