Effective combination immunotherapy using oncolytic viruses to deliver CAR targets to solid tumors

被引：195

作者：

Park, Anthony K. ^{[1
,2
,3
]}

Fong, Yuman ^{[3
]}

Kim, Sang-In ^{[3
]}

Yang, Jason ^{[1
]}

Murad, John P. ^{[1
,2
]}

Lu, Jianming ^{[3
]}

Jeang, Brook ^{[1
]}

Chang, Wen-Chung ^{[1
]}

Chen, Nanhai G. ^{[3
]}

Thomas, Sandra H. ^{[4
]}

Forman, Stephen J. ^{[1
,5
]}

Priceman, Saul J. ^{[1
,5
]}

机构：

[1] City Hope Natl Med Ctr, Dept Hematol & Hematopoiet Cell Transplantat, Duarte, CA 91010 USA

[2] City Hope Natl Med Ctr, Irell & Manella Grad Sch Biol Sci, Duarte, CA 91010 USA

[3] City Hope Natl Med Ctr, Dept Surg, Duarte, CA 91010 USA

[4] City Hope Natl Med Ctr, Dept Clin & Translat Project Dev, Duarte, CA 91010 USA

[5] City Hope Natl Med Ctr, Dept Immunooncol, Beckman Res Inst, Duarte, CA 91010 USA

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2020年 / 12卷 / 559期

基金：

美国国家卫生研究院;

关键词：

CHIMERIC ANTIGEN RECEPTOR; T-CELL THERAPY; PEXA-VEC JX-594; VACCINIA VIRUS; ADOPTIVE TRANSFER; OVARIAN-TUMORS; POXVIRUS; CD19; PHASE-1; ORTHOPOXVIRUS;

D O I：

10.1126/scitranslmed.aaz1863

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Chimeric antigen receptor (CAR)-engineered T cell therapy for solid tumors is limited by the lack of both tumor-restricted and homogeneously expressed tumor antigens. Therefore, we engineered an oncolytic virus to express a nonsignaling, truncated CD19 (CD19t) protein for tumor-selective delivery, enabling targeting by CD19-CAR T cells. Infecting tumor cells with an oncolytic vaccinia virus coding for CD19t (OV19t) produced de novo CD19 at the cell surface before virus-mediated tumor lysis. Cocultured CD19-CART cells secreted cytokines and exhibited potent cytolytic activity against infected tumors. Using several mouse tumor models, delivery of OV19t promoted tumor control after CD19-CART cell administration. OV19t induced local immunity characterized by tumor infiltration of endogenous and adoptively transferred T cells. CART cell-mediated tumor killing also induced release of virus from dying tumor cells, which propagated tumor expression of CD19t. Our study features a combination immunotherapy approach using oncolytic viruses to promote de novo CART cell targeting of solid tumors.

引用

页数：13

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