TY - JOUR
T1 - CD7 CAR T Cells for the Therapy of Acute Myeloid Leukemia
AU - Gomes-Silva, Diogo
AU - Atilla, Erden
AU - Atilla, Pinar Ataca
AU - Mo, Feiyan
AU - Tashiro, Haruko
AU - Srinivasan, Madhuwanti
AU - Lulla, Premal
AU - Rouce, Rayne H.
AU - Cabral, Joaquim M.S.
AU - Ramos, Carlos A.
AU - Brenner, Malcolm
AU - Mamonkin, Maksim
PY - 2019/1/2
Y1 - 2019/1/2
N2 - Chimeric antigen receptor (CAR) T cell therapy for the treatment of acute myeloid leukemia (AML) has the risk of toxicity to normal myeloid cells. CD7 is expressed by the leukemic blasts and malignant progenitor cells of approximately 30% of AML patients but is absent on normal myeloid and erythroid cells. Since CD7 expression by malignant blasts is also linked with chemoresistance and poor outcomes, targeting this antigen may be beneficial for this subset of AML patients. Here, we show that expression of a CD7-directed CAR in CD7 gene-edited (CD7 KO ) T cells effectively eliminates CD7 + AML cell lines, primary CD7 + AML, and colony-forming cells but spares myeloid and erythroid progenitor cells and their progeny. In a xenograft model, CD7 CAR T cells protect mice against systemic leukemia, prolonging survival. Our results support the feasibility of using CD7 KO CD7 CAR T cells for the non-myeloablative treatment of CD7 + AML.
AB - Chimeric antigen receptor (CAR) T cell therapy for the treatment of acute myeloid leukemia (AML) has the risk of toxicity to normal myeloid cells. CD7 is expressed by the leukemic blasts and malignant progenitor cells of approximately 30% of AML patients but is absent on normal myeloid and erythroid cells. Since CD7 expression by malignant blasts is also linked with chemoresistance and poor outcomes, targeting this antigen may be beneficial for this subset of AML patients. Here, we show that expression of a CD7-directed CAR in CD7 gene-edited (CD7 KO ) T cells effectively eliminates CD7 + AML cell lines, primary CD7 + AML, and colony-forming cells but spares myeloid and erythroid progenitor cells and their progeny. In a xenograft model, CD7 CAR T cells protect mice against systemic leukemia, prolonging survival. Our results support the feasibility of using CD7 KO CD7 CAR T cells for the non-myeloablative treatment of CD7 + AML.
KW - CAR T cells
KW - CD7
KW - acute myeloid leukemia
KW - chimeric antigen receptors
KW - mouse model
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UR - http://www.scopus.com/inward/citedby.url?scp=85055730309&partnerID=8YFLogxK
U2 - 10.1016/j.ymthe.2018.10.001
DO - 10.1016/j.ymthe.2018.10.001
M3 - Article
C2 - 30391141
AN - SCOPUS:85055730309
VL - 27
SP - 272
EP - 280
JO - Molecular therapy : the journal of the American Society of Gene Therapy
JF - Molecular therapy : the journal of the American Society of Gene Therapy
SN - 1525-0016
IS - 1
ER -