Oncogene-Targeting T Cells Reject Large Tumors while Oncogene Inactivation Selects Escape Variants in Mouse Models of Cancer

被引：35

作者：

Anders, Kathleen ^{[1
]}

Buschow, Christian ^{[2
]}

Herrmann, Andreas ^{[4
]}

Milojkovic, Ana ^{[5
]}

Loddenkemper, Christoph ^{[3
]}

Kammertoens, Thomas ^{[2
]}

Daniel, Peter ^{[5
]}

Yu, Hua ^{[4
]}

Charo, Jehad ^{[1
]}

Blankenstein, Thomas ^{[1
,2
]}

机构：

[1] Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany

[2] Charite Campus Benjamin Franklin, Inst Immunol, D-12200 Berlin, Germany

[3] Charite Campus Benjamin Franklin, Inst Pathol, D-12200 Berlin, Germany

[4] City Hope Canc Ctr, Beckman Res Inst, Duarte, CA 91010 USA

[5] Charite Campus Berlin Buch, Dept Hematol Oncol & Tumor Immunol, D-13092 Berlin, Germany

来源：

CANCER CELL | 2011年 / 20卷 / 06期

关键词：

ANTIGEN-LOSS VARIANTS; TRANSGENIC MICE; DESTRUCTION; IMMUNOGENICITY; IMMUNOTHERAPY; ANGIOGENESIS; ELIMINATION; ERADICATION; RESISTANCE; EXPRESSION;

D O I：

10.1016/j.ccr.2011.10.019

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The genetic instability of cancer cells frequently causes drug resistance. We established mouse cancer models, which allowed targeting of an oncogene by drug-mediated inactivation or monospecific CD8(+) effector T (T-E) cells. Drug treatment of genetically unstable large tumors was effective but selected resistant clones in the long term. In contrast, T-E cells completely rejected large tumors (>= 500 mm(3)), if the target antigen was cancer-driving and expressed in sufficient amounts. Although drug-mediated oncogene inactivation selectively killed the cancer cells and left the tumor vasculature intact, which likely facilitated survival and growth of resistant clones, T-E cell treatment led to blood vessel destruction and probably "bystander" elimination of escape variants, which did not require antigen cross-presentation by stromal cells.

引用

页码：755 / 767

页数：13

共 46 条

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