Plasmid-Encoded Proinsulin Preserves C-Peptide While Specifically Reducing Proinsulin-Specific CD8+ T Cells in Type 1 Diabetes

Bart O. Roep; Nanette Solvason; Peter A. Gottlieb; Joana R. F. Abreu; Leonard C. Harrison; George S. Eisenbarth; Liping Yu; Michael Leviten; William A. Hagopian; John B. Buse; Matthias von Herrath; Joanne Quan; Robert S. King; William H. Robinson; Paul J. Utz; Hideki Garren; The BHT-3021 Investigators; Lawrence Steinman

doi:10.1126/scitranslmed.3006103

Research ArticleDiabetes

Plasmid-Encoded Proinsulin Preserves C-Peptide While Specifically Reducing Proinsulin-Specific CD8⁺ T Cells in Type 1 Diabetes

Bart O. Roep¹,*,
Nanette Solvason²,³,*,
Peter A. Gottlieb⁴,*,
Joana R. F. Abreu¹,
Leonard C. Harrison⁵,
George S. Eisenbarth⁴,†,
Liping Yu⁴,
Michael Leviten²,
William A. Hagopian⁶,
John B. Buse⁷,
Matthias von Herrath⁸,
Joanne Quan²,
Robert S. King²,
William H. Robinson²,⁹,¹⁰,‡,
Paul J. Utz²,⁹,¹⁰,
Hideki Garren²,¹⁰,
The BHT-3021 Investigators§ and
Lawrence Steinman²,⁹,¹⁰,‡

¹Department for Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
²Bayhill Therapeutics, Palo Alto, CA 94304, USA.
³Foothill College, Los Altos, CA 94022, USA
⁴Barbara Davis Center for Childhood Diabetes, Aurora, CO 80045–6511, USA.
⁵Division of Molecular Medicine, Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria 3052, Australia.
⁶Pacific Northwest Diabetes Research Institute and University of Washington, Seattle, WA 98122, USA.
⁷Diabetes Center for Research, University of North Carolina, Chapel Hill, NC 27599, USA.
⁸La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
⁹Departments of Medicine and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
¹⁰Tolerion Inc., 321 Dedalera Drive, Portola Valley, CA, USA.

↵‡Corresponding author. E-mail: steinman{at}stanford.edu (L.S.); wrobins{at}stanford.edu (W.H.R.)

↵* These authors contributed equally to this work.
↵† Deceased.
↵§ United States: P. Gottlieb, Denver, CO; J. Skyler, Miami, FL; R. Hays, Wellington, FL; F. Ovalle, Birmingham, AL; V. Aroda/R. Ratner, Washington, DC; J. Berg/M. Kipnes, San Antonio, TX; L. Zemel, Denver, CO; M. Rendell, Omaha, NE; P. Norwood, Fresno, CA; P. Raskin, Dallas, TX. Australia/New Zealand: P. Colman, Melbourne; M. Gerstman, Victoria; T. Davis, Fremantle; V. Heazlewood, Queensland; J. Baker, Auckland; P. Dunn, Hamilton; R. Scott, Christchurch; J. Krebs, Wellington. ClinicalTrials.gov registration number: NCT00453375.

See allHide authors and affiliations

Science Translational Medicine 26 Jun 2013:
Vol. 5, Issue 191, pp. 191ra82
DOI: 10.1126/scitranslmed.3006103

Bart O. Roep

1Department for Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Nanette Solvason

2Bayhill Therapeutics, Palo Alto, CA 94304, USA.

3Foothill College, Los Altos, CA 94022, USA

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Peter A. Gottlieb

4Barbara Davis Center for Childhood Diabetes, Aurora, CO 80045–6511, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Joana R. F. Abreu

1Department for Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Leonard C. Harrison

5Division of Molecular Medicine, Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria 3052, Australia.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

George S. Eisenbarth

4Barbara Davis Center for Childhood Diabetes, Aurora, CO 80045–6511, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Liping Yu

4Barbara Davis Center for Childhood Diabetes, Aurora, CO 80045–6511, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Michael Leviten

2Bayhill Therapeutics, Palo Alto, CA 94304, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

William A. Hagopian

6Pacific Northwest Diabetes Research Institute and University of Washington, Seattle, WA 98122, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

John B. Buse

7Diabetes Center for Research, University of North Carolina, Chapel Hill, NC 27599, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Matthias von Herrath

8La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Joanne Quan

2Bayhill Therapeutics, Palo Alto, CA 94304, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Robert S. King

2Bayhill Therapeutics, Palo Alto, CA 94304, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

William H. Robinson

2Bayhill Therapeutics, Palo Alto, CA 94304, USA.

9Departments of Medicine and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.

10Tolerion Inc., 321 Dedalera Drive, Portola Valley, CA, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
For correspondence: steinman@stanford.edu wrobins@stanford.edu

Paul J. Utz

2Bayhill Therapeutics, Palo Alto, CA 94304, USA.

9Departments of Medicine and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.

10Tolerion Inc., 321 Dedalera Drive, Portola Valley, CA, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Hideki Garren

2Bayhill Therapeutics, Palo Alto, CA 94304, USA.

10Tolerion Inc., 321 Dedalera Drive, Portola Valley, CA, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Lawrence Steinman

2Bayhill Therapeutics, Palo Alto, CA 94304, USA.

9Departments of Medicine and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.

10Tolerion Inc., 321 Dedalera Drive, Portola Valley, CA, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
For correspondence: steinman@stanford.edu wrobins@stanford.edu

Article
Figures & Data
Info & Metrics
eLetters
PDF

eLetters is an online forum for ongoing peer review. Submission of eLetters are open to all. Please read our Terms of Service before submitting your own eLetter.

Submit a Response to This Article

Compose eLetter

Title

Contents

More information about text formats

Plain text

Plain text
No HTML tags allowed.
Web page addresses and e-mail addresses turn into links automatically.
Lines and paragraphs break automatically.

Author Information

Contributors
First name and middle name First or given name, e.g. 'Peter'. Last Name Your last, or family, name, e.g. 'MacMoody'. Email Your email address, e.g. higgs-boson@gmail.com Role / Occupation Your role and/or occupation, e.g. 'Orthopedic Surgeon'. Affiliation Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.

Statement of Competing Interests

Competing interests?

Yes

Please describe the competing interests

CAPTCHA

This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

No eLetters have been published for this article.

View Full Text

Plasmid-Encoded Proinsulin Preserves C-Peptide While Specifically Reducing Proinsulin-Specific CD8⁺ T Cells in Type 1 Diabetes

Plain text

Vertical Tabs

Science Translational Medicine

Article Tools