Targeting Cancer with a Lupus Autoantibody

James E. Hansen; Grace Chan; Yanfeng Liu; Denise C. Hegan; Shibani Dalal; Eloise Dray; Youngho Kwon; Yuanyuan Xu; Xiaohua Xu; Elizabeth Peterson-Roth; Erik Geiger; Yilun Liu; Joseph Gera; Joann B. Sweasy; Patrick Sung; Sara Rockwell; Robert N. Nishimura; Richard H. Weisbart; Peter M. Glazer

doi:10.1126/scitranslmed.3004385

Research ArticleCancer

Targeting Cancer with a Lupus Autoantibody

James E. Hansen¹,²,*,
Grace Chan³,
Yanfeng Liu¹,
Denise C. Hegan¹,
Shibani Dalal¹,
Eloise Dray⁴,†,
Youngho Kwon⁴,
Yuanyuan Xu⁴,
Xiaohua Xu⁵,
Elizabeth Peterson-Roth¹,
Erik Geiger¹,
Yilun Liu⁵,
Joseph Gera³,⁶,
Joann B. Sweasy¹,²,⁷,⁸,
Patrick Sung¹,²,⁴,
Sara Rockwell¹,²,⁹,
Robert N. Nishimura³,¹⁰,
Richard H. Weisbart³ and
Peter M. Glazer¹,²,⁸,*

¹Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520, USA.
²Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, USA.
³Veterans Affairs Greater Los Angeles Healthcare System, Sepulveda, CA 91343, USA.
⁴Department of Molecular Biophysics and Biochemistry, Yale School of Medicine, New Haven, CT 06520, USA.
⁵Division of Radiation Biology, Beckman Research Institute, Duarte, CA 91010, USA.
⁶David Geffen School of Medicine, Jonsson Comprehensive Cancer Center, and Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁷Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA.
⁸Department of Genetics, Yale School of Medicine, New Haven, CT 06520, USA.
⁹Department of Pharmacology, Yale School of Medicine, New Haven, CT 06520, USA.
¹⁰Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.

↵*To whom correspondence should be addressed. E-mail: james.e.hansen{at}yale.edu (J.E.H.); peter.glazer{at}yale.edu (P.M.G.)

↵† Present address: Australian Institute for Bioengineering and Nanotechnology (AIBN), University of Queensland, St Lucia 4072, Queensland, Australia.

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Science Translational Medicine 24 Oct 2012:
Vol. 4, Issue 157, pp. 157ra142
DOI: 10.1126/scitranslmed.3004385

James E. Hansen

1Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520, USA.

2Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, USA.

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For correspondence: james.e.hansen@yale.edu peter.glazer@yale.edu

Grace Chan

3Veterans Affairs Greater Los Angeles Healthcare System, Sepulveda, CA 91343, USA.

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Yanfeng Liu

1Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520, USA.

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Denise C. Hegan

1Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520, USA.

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Shibani Dalal

1Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520, USA.

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Eloise Dray

4Department of Molecular Biophysics and Biochemistry, Yale School of Medicine, New Haven, CT 06520, USA.

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Youngho Kwon

4Department of Molecular Biophysics and Biochemistry, Yale School of Medicine, New Haven, CT 06520, USA.

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Yuanyuan Xu

4Department of Molecular Biophysics and Biochemistry, Yale School of Medicine, New Haven, CT 06520, USA.

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Xiaohua Xu

5Division of Radiation Biology, Beckman Research Institute, Duarte, CA 91010, USA.

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Elizabeth Peterson-Roth

1Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520, USA.

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Erik Geiger

1Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520, USA.

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Yilun Liu

5Division of Radiation Biology, Beckman Research Institute, Duarte, CA 91010, USA.

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Joseph Gera

3Veterans Affairs Greater Los Angeles Healthcare System, Sepulveda, CA 91343, USA.

6David Geffen School of Medicine, Jonsson Comprehensive Cancer Center, and Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.

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Joann B. Sweasy

1Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520, USA.

2Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, USA.

7Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA.

8Department of Genetics, Yale School of Medicine, New Haven, CT 06520, USA.

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Patrick Sung

1Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520, USA.

2Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, USA.

4Department of Molecular Biophysics and Biochemistry, Yale School of Medicine, New Haven, CT 06520, USA.

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Sara Rockwell

1Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520, USA.

2Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, USA.

9Department of Pharmacology, Yale School of Medicine, New Haven, CT 06520, USA.

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Robert N. Nishimura

3Veterans Affairs Greater Los Angeles Healthcare System, Sepulveda, CA 91343, USA.

10Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.

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Richard H. Weisbart

3Veterans Affairs Greater Los Angeles Healthcare System, Sepulveda, CA 91343, USA.

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Peter M. Glazer

1Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520, USA.

2Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, USA.

8Department of Genetics, Yale School of Medicine, New Haven, CT 06520, USA.

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For correspondence: james.e.hansen@yale.edu peter.glazer@yale.edu

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A cell-penetrating lupus anti-DNA antibody inhibits DNA repair, sensitizes cancer cells to DNA-damaging therapy in vitro and in vivo, and is synthetically lethal to BRCA2-deficient human cancer cells.

Targeting Cancer with a Lupus Autoantibody

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