GRP78-CAR T cell effector function against solid and brain tumors is controlled by GRP78 expression on T cells

• DOI: 10.1016/j.xcrm.2023.101297
• Publication Date: 2023-11-21T16:36:30Z
• Authors: Jorge Ibanez; Nikhil Hebbar; Unmesha Thanekar; Zhongzhen Yi; Haley Houke; Meghan Ward; Chris Nevitt; Liqing Tian; Stephen C. Mack; Heather Sheppard; Jason Chiang; M. Paulina Velasquez; Giedre Krenciute
• Keywords: Cancer Immunotherapy

Lack of targetable antigens is a key limitation for developing successful T cell-based immunotherapies. Members the unfolded protein response (UPR) represent ideal immunotherapy targets because UPR regulates ability cancer cells to resist cell death, sustain proliferation, and metastasize. Glucose-regulated 78 (GRP78) regulator that overexpressed translocated surface wide variety cancers in elevated endoplasmic reticulum (ER) stress. We show GRP78 highly expressed on multiple solid brain tumors, making promising chimeric antigen receptor (CAR) target. demonstrate GRP78-CAR can recognize kill GRP78+ tumors vitro vivo. Additionally, our findings upregulated CAR upon activation; however, this expression tumor-cell-line specific results heterogeneous therapeutic response.