Genetically engineered T cells to target EGFRvIII expressing glioblastoma

被引：55

作者：

Bullain, Szofia S. ^{[1
]}

Sahin, Ayguen ^{[1
]}

Szentirmai, Oszkar ^{[1
]}

Sanchez, Carlos ^{[1
]}

Lin, Ning ^{[1
]}

Baratta, Elizabeth ^{[1
]}

Waterman, Peter ^{[2
]}

Weissleder, Ralph ^{[2
]}

Mulligan, Richard C. ^{[3
]}

Carter, Bob S. ^{[1
]}

机构：

[1] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA

[2] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA

[3] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA

来源：

JOURNAL OF NEURO-ONCOLOGY | 2009年 / 94卷 / 03期

关键词：

Adoptive immunotherapy; Glioma; Chimeric immune receptor; Chimeric T cell receptor; EGFRvIII; MR1; ANTIGEN RECEPTOR; GROWTH; CD28; IMMUNOTHERAPY; IMMUNOTOXINS; VACCINATION; MOLECULES; DEFECTS; THERAPY; PROTEIN;

D O I：

10.1007/s11060-009-9889-1

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Glioblastoma remains a significant therapeutic challenge, warranting further investigation of novel therapies. We describe an immunotherapeutic strategy to treat glioblastoma based on adoptive transfer of genetically modified T-lymphocytes (T cells) redirected to kill EGFRvIII expressing gliomas. We constructed a chimeric immune receptor (CIR) specific to EGFRvIII, (MR1-zeta). After in vitro selection and expansion, MR1-zeta genetically modified primary human T-cells specifically recognized EGFRvIII-positive tumor cells as demonstrated by IFN-gamma secretion and efficient tumor lysis compared to control CIRs defective in EGFRvIII binding (MRB-zeta) or signaling (MR1-del zeta). MR1-zeta expressing T cells also inhibited EGFRvIII-positive tumor growth in vivo in a xenografted mouse model. Successful targeting of EGFRvIII-positive tumors via adoptive transfer of genetically modified T cells may represent a new immunotherapy strategy with great potential for clinical applications.

引用

页码：373 / 382

页数：10

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