CD137 agonist antibody prevents cancer recurrence: contribution of CD137 on both hematopoietic and nonhematopoietic cells

被引:40
|
作者
Narazaki, Hidehiko
Zhu, Yuwen
Luo, Liqun
Zhu, Gefeng
Chen, Lieping
机构
[1] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA
基金
美国国家卫生研究院;
关键词
TUMOR-INFILTRATING LYMPHOCYTES; MONOCLONAL-ANTIBODIES; T-LYMPHOCYTES; RECEPTOR SUPERFAMILY; IMMUNITY; IMMUNOTHERAPY; ACTIVATION; EXPRESSION; ANTIGEN; MICE;
D O I
10.1182/blood-2008-12-192591
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Antigen-specific memory T cells (Tms) are essential in the immune surveillance of residual and metastatic tumors. Activation of Tms requires designing vaccines based on tumor rejection antigens, which are often not available to cancer patients. Therefore, it is desirable to have a general applicable approach to activate Tms without extensive knowledge of tumor antigens. Here, we report that activation of antigen-specific Tms could be achieved by the administration of agonistic anti-CD137 monoclonal antibody without additional tumor vaccination, leading to the prevention of recurrence and metastases after surgical resection of primary tumors in mouse models. By reconstitution with CD137-deficient Tms, we demonstrate that expression of CD137 on antigen-specific Tms is only partially required for the effect of anti-CD137 antibody. Other host cells, including those from hematopoietic and nonhematopoietic origins, are also important because ablation of CD137 from these cells partially but significantly eliminates antitumor effect of anti-CD137 antibody. Our findings implicate a potential new approach to prevent recurrence and metastases in cancer patients. (Blood. 2010; 115: 1941-1948)
引用
收藏
页码:1941 / 1948
页数:8
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