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

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

Molecular Therapy: Oncology (Sep 2024)

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

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

Affiliations

Christopher S. Hackett: Department 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
Daniel Hirschhorn: 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
Meixian S. Tang: 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
Terence J. Purdon: Roswell Park Cancer Center, Buffalo, NY 14203, USA
Yacine Marouf: 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
Alessandra Piersigilli: Laboratory of Comparative Pathology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, The Rockefeller University, New York, NY 10065, USA
Narasimhan P. Agaram: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Cailian Liu: 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
Sara E. Schad: 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
Elisa de Stanchina: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Sarwish Rafiq: Department of Hematology and Medical Oncology, Emory University School of Medicine, and Winship Cancer Institute, Atlanta, GA 30322, USA
Sebastien Monette: Laboratory of Comparative Pathology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, The Rockefeller University, New York, NY 10065, USA
Jedd D. Wolchok: Department 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.
Taha Merghoub: 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.
Renier J. Brentjens: Roswell Park Cancer Center, Buffalo, NY 14203, USA; Corresponding author: Renier J. Brentjens, Roswell Park Cancer Center, Buffalo, NY 14203, USA.

Journal volume & issue: Vol. 32, no. 3
p. 200862

Abstract

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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.

Published in Molecular Therapy: Oncology

ISSN: 2950-3299 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.cell.com/molecular-therapy-family/oncology/home

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