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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Campa, MJ; Gottlin, EB; Bushey, RT; Patz, EF

Published Date

  • December 2015

Published In

Volume / Issue

  • 3 / 12

Start / End Page

  • 1325 - 1332

PubMed ID

  • 26216416

Pubmed Central ID

  • 26216416

Electronic International Standard Serial Number (EISSN)

  • 2326-6074

Digital Object Identifier (DOI)

  • 10.1158/2326-6066.CIR-15-0122

Language

  • eng

Conference Location

  • United States