TYRP1 directed CAR T cells control tumor progression in preclinical melanoma models Journal Article

   


Authors: Hackett, C. S.; Hirschhorn, D.; Tang, M. S.; Purdon, T. J.; Marouf, Y.; Piersigilli, A.; Agaram, N. P.; Liu, C.; Schad, S. E.; de Stanchina, E.; Rafiq, S.; Monette, S.; Wolchok, J. D.; Merghoub, T.; Brentjens, R. J.
Article Title: TYRP1 directed CAR T cells control tumor progression in preclinical melanoma models
Abstract: 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 CART 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.
Keywords: melanocytes; antigen; adoptive transfer; management; solid tumors; resistance; differentiation; expression; clinical-efficacy; nivolumab
Journal Title: Molecular Therapy - Oncology
Volume: 32
Issue: 3
ISSN: 2950-3299
Publisher: Cell Press  
Date Published: 2024-09-19
Start Page: 200862
Language: English
ACCESSION: WOS:001314891100001
DOI: 10.1016/j.omton.2024.200862
PROVIDER: wos
PMCID: PMC11415964
PUBMED: 39308793
Notes: The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Source: Wos
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MSK Authors
  1. Narasimhan P Agaram
    190 Agaram
  2. Sebastien Monette
    148 Monette
  3. Elisa De Stanchina
    343 De Stanchina
  4. Alessandra Piersigilli
    15 Piersigilli
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