Complement Factor H Antibodies from Lung Cancer Patients Induce Complement-Dependent Lysis of Tumor Cells, Suggesting a Novel Immunotherapeutic Strategy

被引:37
作者
Campa, Michael J. [1 ]
Gottlin, Elizabeth B. [1 ]
Bushey, Ryan T. [1 ]
Patz, Edward F., Jr. [1 ,2 ]
机构
[1] Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA
[2] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA
关键词
HEMOLYTIC-UREMIC SYNDROME; AUTOIMMUNE FORM; C3B; AUTOANTIBODIES; EXPRESSION; RESISTANCE; PROTEINS; VACCINES; BINDING;
D O I
10.1158/2326-6066.CIR-15-0122
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Characterization of the humoral immune response in selected patients with cancer who uniformly do well may lead to the development of novel therapeutic strategies. We have previously shown an association between patients with early-stage nonmetastatic lung cancer and autoantibodies to complement factor H (CFH). CFH protects normal and tumor cells from destruction by the alternative complement pathway by inactivating C3b, a protein that is essential for formation of a lytic complex on the cell surface. Here, we show that CFH autoantibodies in lung cancer patients recognize a conformationally distinct form of CFH in vitro, are IgG3 subclass, and epitope map to a crucial functional domain of CFH known to interact with C3b. Purified CFH autoantibodies inhibited binding of CFH to A549 lung tumor cells, increased C3b deposition, and caused complement-dependent tumor cell lysis. This work demonstrates that CFH autoantibodies isolated from patients with lung cancer can kill tumor cells in vitro, suggesting that they may perform this function in vivo as well. Development of specific antibodies to the conformationally distinct epitope of CFH may lead to a useful biologic therapy for lung cancer. (C)2015 AACR.
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收藏
页码:1325 / 1332
页数:8
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