Engagement of the OX-40 receptor in vivo enhances antitumor immunity

被引:313
作者
Weinberg, AD
Rivera, MM
Prell, R
Morris, A
Ramstad, T
Vetto, JT
Urba, WJ
Alvord, G
Bunce, C
Shields, J
机构
[1] Robert W Franz Canc Res Ctr, Earle A Chiles Res Inst, Prov Portland Med Ctr, Portland, OR 97213 USA
[2] Oregon Hlth Sci Univ, Dept Surg, Sect Surg Oncol, Portland, OR 97201 USA
[3] Cantab Pharmaceut, Cambridge, England
[4] NCI, Comp Serv, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA
[5] NCI, Stat Serv, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA
关键词
D O I
10.4049/jimmunol.164.4.2160
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The OX-40 receptor (OX-40R), a member of the TNFR family, is primarily expressed on activated CD4(+) T lymphocytes. Engagement of the OX-40R, with either OX-40 ligand (OX-40L) or an Ab agonist, delivers a strong costimulatory signal to effector T cells. OX-40R(+) T cells isolated from inflammatory lesions in the CNS of animals with experimental autoimmune encephalomyelitis are the cells that respond to autoantigen (myelin basic protein) in vivo. We identified OX-40R(+) T cells within primary tumors and tumor-invaded lymph nodes of patients with cancer and hypothesized that they are the tumor-Ag-specific T cells. Therefore, we investigated whether engagement of the OX-40R in vivo during tumor priming would enhance a tumor-specific T cell response. Injection of OX-40L:Ig or anti-OX-40R in vivo during tumor priming resulted in a significant improvement in the percentage of tumor-free survivors (20-55%) in four different murine tumors derived from four separate tissues. This anti-OX-40R effect was dose dependent and accentuated tumor-specific T cell memory. The data suggest that engagement of the OX-40R in vivo augments tumor-specific priming by stimulating/expanding the natural repertoire of the host's tumor-specific CD4(+) T cells. The identification of OX-40R(+) T cells clustered around human tumor cells in vivo suggests that engagement of the OX-40R may be a practical approach for expanding tumor-reactive T cells and thereby a method to improve tumor immunotherapy in patients with cancer.
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页码:2160 / 2169
页数:10
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