GPC2-CAR T cells tuned for low antigen density mediate potent activity against neuroblastoma without toxicity

• DOI: 10.1016/j.ccell.2021.12.005
• Publication Date: 2021-12-30T15:31:25Z
• Authors: Sabine Heitzeneder; Kristopher R. Bosse; Zhongyu Zhu; Doncho Zhelev; Robbie G. Majzner; Molly T. Radosevich; Shaurya Dhingra; Elena Sotillo; Samantha Buongervino; Guillem Pascual-P...; Emily Garrigan; Peng Xu; Jing Huang; Benjamin Salzer; Alberto Delaidelli; Swetha Raman; Hong Cui; Benjamin Martinez; Scott J. Bornheimer; Bita Sahaf; Anya Alag; Irfete S. Fetahu; Martin Hasselblatt; Kevin R. Parker; Hima Anbunathan; Jennifer Hwang; Min Huang; Kathleen Sakamoto; Norman J. Lacayo; Dorota D. Klysz; Johanna Theruvath; José G. Vilches-M...; Ansuman T. Satpathy; Howard Y. Chang; Manfred Lehner; Sabine Taschner-M...; Jean-Phillipe Julien; Poul H. Sorensen; Dimiter S. Dimitrov; John M. Maris; Crystal L. Mackall
• Keywords: Neuroblastoma; Receptors, Chimeric Antigen; Glypicans; Cell Line, Tumor; T-Lymphocytes; Receptors, Antigen, T-Cell; Animals; Humans; Immunotherapy; Immunotherapy, Adoptive; Xenograft Model Antitumor Assays; 3. Good health

Pediatric cancers often mimic fetal tissues and express proteins normally silenced postnatally that could serve as immune targets. We developed T cells expressing chimeric antigen receptors (CARs) targeting glypican-2 (GPC2), a expressed on neuroblastoma (NB) several other solid tumors. CARs engineered using standard designs control NBs with transgenic GPC2 overexpression, but not those clinically relevant site density (∼5,000 molecules/cell, range 1-6 × 10