Induction of resistance to chimeric antigen receptor T cell therapy by transduction of a single leukemic B cell

被引：501

作者：

Ruella, Marco ^{[1
,2
,3
,4
,5
]}

Xu, Jun ^{[1
,2
,3
]}

Barrett, David M. ^{[6
]}

Fraietta, Joseph A. ^{[1
,2
,3
,4
]}

Reich, Tyler J. ^{[1
]}

Ambrose, David E. ^{[1
]}

Klichinsky, Michael ^{[1
,7
]}

Shestova, Olga ^{[1
]}

Patel, Prachi R. ^{[1
]}

Kulikovskaya, Irina ^{[1
]}

Nazimuddin, Farzana ^{[1
]}

Bhoj, Vijay G. ^{[1
,2
,3
]}

Orlando, Elena J. ^{[8
]}

Fry, Terry J. ^{[9
]}

Bitter, Hans ^{[8
]}

Maude, Shannon L. ^{[6
]}

Levine, Bruce L. ^{[1
,2
,3
]}

Nobles, Christopher L. ^{[10
]}

Bushman, Frederic D. ^{[10
]}

Young, Regina M. ^{[1
]}

Scholler, John ^{[1
]}

Gill, Saar I. ^{[1
,3
,5
]}

June, Carl H. ^{[1
,2
,3
,4
]}

Grupp, Stephan A. ^{[6
]}

Lacey, Simon F. ^{[1
,2
,3
]}

Melenhorst, J. Joseph ^{[1
,2
,3
]}

机构：

[1] Univ Penn, Perelman Sch Med, Ctr Cellular Immunotherapies, Philadelphia, PA 19104 USA

[2] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA 19104 USA

[3] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA

[4] Univ Penn, Parker Inst Cellular Immunotherapy, Philadelphia, PA 19104 USA

[5] Univ Penn, Dept Med, Div Hematol Oncol, Perelman Sch Med, Philadelphia, PA 19104 USA

[6] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA

[7] Univ Penn, Perelman Sch Med, Dept Syst Pharmacol & Translat Therapeut, Philadelphia, PA 19104 USA

[8] Novartis Inst Biomed Res, Cambridge, MA USA

[9] Univ Colorado, Childrens Hosp Colorado, Denver, CO 80202 USA

[10] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA

来源：

NATURE MEDICINE | 2018年 / 24卷 / 10期

基金：

美国国家卫生研究院;

关键词：

TUMOR-CELLS; FRAMEWORK;

D O I：

10.1038/s41591-018-0201-9

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We report a patient relapsing 9 months after CD19-targeted CAR T cell (CTLO19) infusion with CD19(-) leukemia that aberrantly expressed the anti-CD19 CAR. The CAR gene was unintentionally introduced into a single leukemic B cell during T cell manufacturing, and its product bound in cis to the CD19 epitope on the surface of leukemic cells, masking it from recognition by and conferring resistance to CTLO19.

引用

页码：1499 / +

页数：7

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