AUTHOR=Yu Wei , Zhang Hang , Yuan Yuncang , Tang Jie , Chen Xinchuan , Liu Ting , Zhao Xudong TITLE=Chimeric Antigen Receptor T Cells Targeting Cell Surface GRP78 to Eradicate Acute Myeloid Leukemia JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=10 YEAR=2022 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.928140 DOI=10.3389/fcell.2022.928140 ISSN=2296-634X ABSTRACT=

Acute myeloid leukemia (AML) is a serious, life-threatening hematological malignancy. The treatment outcome of relapsed or refractory AML patients remains dismal, and new treatment options are needed. Chimeric antigen receptor (CAR) T cells have been successful in improving the prognosis for B-lineage acute lymphoblastic leukemia and lymphoma by targeting CD19. However, CAR T-cell therapy for AML is still elusive, owing to the lack of a tumor-specific cell surface antigen and spare hematopoietic stem cells (HSCs). This study generated a novel CAR construction that targets the cell surface protein glucose-regulated protein 78 (GRP78) (csGRP78). We confirmed that GRP78-CAR T cells demonstrate an anti-tumor effect against human AML cells in vitro. In xenograft models, GRP78-CAR T cells effectively eliminate AML cells and protect mice against systemic leukemia, in the meanwhile, prolonging survival. In addition, GRP78-CAR T cells also specifically eradicate the primary AML patient-derived blast. In particular, GRP78-CAR T cells spare normal HSCs, highlighting that GRP78-CAR is a promising approach for the therapy of AML.