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 the surface of melanomas, including rare acral and uveal melanomas. TYRP1-targeted CAR T cells demonstrate antigen-specific activation and cytotoxic activity <i>in vitro</i> and <i>in vivo</i> 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.
Authors
- Taha Merghoub (ORCID: https://orcid.org/0000-0002-1518-5111)
- Elisa de Stanchina (ORCID: https://orcid.org/0000-0002-3873-315X)
- Sara Schad (ORCID: https://orcid.org/0000-0002-2306-6999)
- Christopher S. Hackett (ORCID: https://orcid.org/0000-0003-4692-2433)
- Daniel Hirschhorn (ORCID: https://orcid.org/0000-0003-0467-7687)
- Alessandra Piersigilli
- Narasimhan P. Agaram (ORCID: https://orcid.org/0000-0002-6991-2310)
- Jedd D. Wolchok (ORCID: https://orcid.org/0000-0001-6718-2222)
- Sarwish Rafiq (ORCID: https://orcid.org/0000-0002-9295-3065)
- Sébastien Monette (ORCID: https://orcid.org/0000-0003-2841-6887)
- Renier J. Brentjens (ORCID: https://orcid.org/0000-0002-3364-5388)
- Cailian Liu
- Yacine Marouf (ORCID: https://orcid.org/0000-0002-4621-1407)
- Terence J. Purdon (ORCID: https://orcid.org/0009-0009-7824-7760)
- Meixian S Tang
Institutions
- Roswell Park Comprehensive Cancer Center (US)
- Memorial Sloan Kettering Cancer Center (US)
- Emory University (US)
- Cornell University (US)
- Swim Across America (US)
- Parker Institute for Cancer Immunotherapy (US)
- Weill Cornell Medicine (US)
Publication Details
- Journal
- Molecular Therapy Oncology
- Published
- 2024-08-23
- DOI
- https://doi.org/10.1016/j.omton.2024.200862
- Citations
- 7
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 1.98
Funders
- U.S. Department of Defense
- Breast Cancer Research Foundation
- Melanoma Research Alliance
- Ludwig Institute for Cancer Research
- Parker Institute for Cancer Immunotherapy
- Swim Across America
- National Institutes of Health
- Stand Up To Cancer
- National Cancer Institute