Characterization of the humoral immune response in select cancer patients who uniformly do well may lead to the development of novel therapeutic strategies. We have previously shown an association between patients with early stage non-metastatic 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 lung cancer patients can kill tumor cells in vitro, suggesting 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.
- Received May 5, 2015.
- Revision received July 1, 2015.
- Accepted July 3, 2015.
- Copyright © 2015, American Association for Cancer Research.