Targeting cancer with a lupus autoantibody

Hansen, James E., Chan, Grace, Liu, Yanfeng, Hegan, Denise C., Dalal, Shibani, Dray, Eloise, Kwon, Youngho, Xu, Yuanyuan, Xu, Xiaohua, Peterson-Roth, Elizabeth, Geiger, Erik, Liu, Yilun, Gera, Joseph, Sweasy, Joann B., Sung, Patrick, Rockwell, Sara, Nishimura, Robert N., Weisbart, Richard H. and Glazer, Peter M. (2012) Targeting cancer with a lupus autoantibody. Science Translational Medicine, 4 157: . doi:10.1126/scitranslmed.3004385


Author Hansen, James E.
Chan, Grace
Liu, Yanfeng
Hegan, Denise C.
Dalal, Shibani
Dray, Eloise
Kwon, Youngho
Xu, Yuanyuan
Xu, Xiaohua
Peterson-Roth, Elizabeth
Geiger, Erik
Liu, Yilun
Gera, Joseph
Sweasy, Joann B.
Sung, Patrick
Rockwell, Sara
Nishimura, Robert N.
Weisbart, Richard H.
Glazer, Peter M.
Title Targeting cancer with a lupus autoantibody
Journal name Science Translational Medicine   Check publisher's open access policy
ISSN 1946-6234
1946-6242
Publication date 2012-10-24
Sub-type Article (original research)
DOI 10.1126/scitranslmed.3004385
Open Access Status
Volume 4
Issue 157
Total pages 8
Place of publication Washington, DC United States
Publisher American Association for the Advancement of Science
Subject 2700 Medicine
Abstract Systemic lupus erythematosus (SLE) is distinct among autoimmune diseases because of its association with circulating autoantibodies reactive against host DNA. The precise role t hat anti-DNA antibodies play in SLE patho- physiology remains to be elucidated, and potential appl ications of lupus autoantibodies in cancer therapy have not previously been explored. We report t he unexpected finding that a cell-penetrating lupus autoantibody, 3E10, has potential as a targeted therapy for DNA repair – deficient malignancies. We find that 3E10 preferentially binds DNA single-strand tails, inhibits key steps inDNAsingle-strandanddouble-strandb reak repair, and sensitizes cultured tumor cells and human tumor xenografts to DNA-damaging t herapy, including doxorubicin and radiation. More- over, we demonstrate that 3E10 alone is synthetically let hal to BRCA2-deficient human cancer cells and selectively sensitizes such cells to low-dose doxo rubicin. Our results establish an app roach to cancer therapy that we expect will be particularly applicable to BRCA2-related malignancies such as breast, ovarian, and prostate cancers. In addition, our findings raise the possibility that lupus autoantibodies may be partly responsible for the intrinsic deficiencies in DNA repair and the unexpectedly low rates of breast, ovarian, and prostate cancers observed in SLE patients. In summary, this study provides the basis for the potential use of a lupus anti-DNA antibody in cancer therapy and identifies lupus autoantibodies as a potentially rich source of therapeutic agents.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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