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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Bibliographic Details
Published in:Molecular Therapy: Oncology 2024-09, Vol.32 (3), p.200862, Article 200862
Main Authors: Hackett, Christopher S, Hirschhorn, Daniel, Tang, Meixian S, Purdon, Terence J, Marouf, Yacine, Piersigilli, Alessandra, Agaram, Narasimhan P, Liu, Cailian, Schad, Sara E, de Stanchina, Elisa, Rafiq, Sarwish, Monette, Sebastien, Wolchok, Jedd D, Merghoub, Taha, Brentjens, Renier J
Format: Article
Language:English
Subjects:
acral
adoptive cellular therapy
chimeric antigen receptor
melanoma
MT: Regular Issue
Original
uveal
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Summary: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 and 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.
ISSN:2950-3299
2950-3299
DOI:10.1016/j.omton.2024.200862