CD7 CAR T Cells for the Therapy of Acute Myeloid Leukemia

被引：117

作者：

Gomes-Silva, Diogo ^{[1
,2
,3
]}

Atilla, Erden ^{[1
]}

Atilla, Pinar Ataca ^{[1
]}

Mo, Feiyan ^{[1
,4
]}

Tashiro, Haruko ^{[1
]}

Srinivasan, Madhuwanti ^{[1
]}

Lulla, Premal ^{[1
]}

Rouce, Rayne H. ^{[1
,5
]}

Cabral, Joaquim M. S. ^{[2
,3
]}

Ramos, Carlos A. ^{[1
]}

Brenner, Malcolm K. ^{[1
,6
]}

Mamonkin, Maksim ^{[1
,6
]}

机构：

[1] Houston Methodist Hosp, Texas Childrens Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA

[2] Univ Lisbon, Inst Super Tecn, Dept Bioengn, Lisbon, Portugal

[3] Univ Lisbon, Inst Super Tecn, Inst Bioengn & Biosci, Lisbon, Portugal

[4] Baylor Coll Med, Interdept Grad Program Translat Biol & Mol Med, Houston, TX 77030 USA

[5] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA

[6] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA

来源：

MOLECULAR THERAPY | 2019年 / 27卷 / 01期

关键词：

CHIMERIC ANTIGEN RECEPTOR; STEM-CELLS; CLINICAL-SIGNIFICANCE; DENDRITIC CELLS; NATURAL-KILLER; EXPRESSION; PROGENITOR; HIERARCHY; IDENTIFICATION; BLASTS;

D O I：

10.1016/j.ymthe.2018.10.001

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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.

引用

页码：272 / 280

页数：9

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