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

Department 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

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

Barbara 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

Department 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

Division 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

Barbara 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

Barbara 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

Bayhill 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

Pacific 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

Diabetes 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

La 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

Bayhill 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

Bayhill 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

Bayhill Therapeutics, Palo Alto, CA 94304, USA.Departments of Medicine and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.Tolerion 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.eduwrobins@stanford.edu

Paul J. Utz

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

Hideki Garren

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

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

What code is in the image? Enter the characters shown in the image.

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