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=Volume 10 - 2022

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 T cells (CART) have been successful in improving prognosis for B-lineage acute lymphoblastic leukemia and lymphoma by targeting CD19. However, CAR-T therapy for AML is still elusive, owing to the lack of tumor-specific cell surface antigen and spare hematopoietic stem cells (HSCs) in the meanwhile. Here, we generated a novel CAR construction that targets the cell surface protein GRP78 (csGRP78). We confirmed the 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. Importantly, GRP78-CAR T cells spare normal HSCs, highlighting GRP78-CAR is a promising approach for the therapy of AML.