Mechanostimulatory Platform for Improved CAR T Cell Immunotherapy
Abstract
AbstractChimeric Antigen Receptor T (CAR T) cell immunotherapy has revolutionized cancer treatment, yet it is hindered by rapid T‐cell exhaustion caused by uncontrolled activation during CAR generation. Leveraging insights into T‐cell mechanosensing, a novel mechanostimulatory platform is engineered for T‐cell activation based on an antigen‐carrying surface with controlled elasticity and nanotopography. The platform is designed to optimize and balance T‐cell exhaustion, proliferation, and CAR expression. It enhances the differentiation of T cells into the central memory subset, which is crucial for the persistence of CAR T cell therapy's anticancer effects. The platform produces CAR T cells with higher antitumor efficacy, as validated through ex vivo experiments, and with higher in vivo persistence and ability to suppress tumor proliferation, as compared to CAR T cells generated by standard protocols. RNA‐seq analysis confirmed an increased transcriptional signature of central memory T cells. Furthermore, this platform completely eliminates T‐cell toxicity associated with the non‐viral transfection process typically observed with standard activation methods. This platform presents a promising pathway for improving the efficiency and safety of CAR T cell therapy.
Article Details
Authors (21)
Abed Al‐Kader Yassin
The Shraga Segal Department of Microbiology Immunology, and Genetics Faculty of Health Sciences Ben‐Gurion University of the Negev Beer‐Sheva 8410501 Israel
Carlos Ureña Martin
Department of Materials Engineering Faculty of Engineering Ben‐Gurion University of the Negev Beer‐Sheva 8410501 Israel
Guillaume Le Saux
Department of Materials Engineering Faculty of Engineering Ben‐Gurion University of the Negev Beer‐Sheva 8410501 Israel
Ashish Pandey
Sivan Tzadka
Department of Materials Engineering Faculty of Engineering Ben‐Gurion University of the Negev Beer‐Sheva 8410501 Israel
Esti Toledo
Department of Materials Engineering Faculty of Engineering Ben‐Gurion University of the Negev Beer‐Sheva 8410501 Israel
Jatin Jawhir Pandit
Department of Materials Engineering Faculty of Engineering Ben‐Gurion University of the Negev Beer‐Sheva 8410501 Israel
Tomer Sherf
Department of Materials Engineering Faculty of Engineering Ben‐Gurion University of the Negev Beer‐Sheva 8410501 Israel
Idan Nusbaum
Department of Materials Engineering Faculty of Engineering Ben‐Gurion University of the Negev Beer‐Sheva 8410501 Israel
Baisali Bhattachrya
The Shraga Segal Department of Microbiology Immunology, and Genetics Faculty of Health Sciences Ben‐Gurion University of the Negev Beer‐Sheva 8410501 Israel
Rajashri Banerji
The Shraga Segal Department of Microbiology Immunology, and Genetics Faculty of Health Sciences Ben‐Gurion University of the Negev Beer‐Sheva 8410501 Israel
Yariv Greenshpan
The Shraga Segal Department of Microbiology Immunology, and Genetics Faculty of Health Sciences Ben‐Gurion University of the Negev Beer‐Sheva 8410501 Israel
Muhammad Abu Abu Ahmad
The Shraga Segal Department of Microbiology Immunology, and Genetics Faculty of Health Sciences Ben‐Gurion University of the Negev Beer‐Sheva 8410501 Israel
Olga Radinsky
The Shraga Segal Department of Microbiology Immunology, and Genetics Faculty of Health Sciences Ben‐Gurion University of the Negev Beer‐Sheva 8410501 Israel
Menachem Sklartz
The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev
Roi Gazit
The Shraga Segal Department of Microbiology Immunology, and Genetics Faculty of Health Sciences Ben‐Gurion University of the Negev Beer‐Sheva 8410501 Israel
Moshe Elkabets
The Shraga Segal Department of Microbiology Immunology, and Genetics Faculty of Health Sciences Ben‐Gurion University of the Negev Beer‐Sheva 8410501 Israel
Saba Ghassemi
Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia
Ofir Cohen
The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev
Mark Schvartzman
Department of Materials Engineering Faculty of Engineering Ben‐Gurion University of the Negev Beer‐Sheva 8410501 Israel
Angel Porgador
The Shraga Segal Department of Microbiology, Immunology and Genetics, Ben-Gurion University of the Negev