VACCINE: AUTO-IMMUNE DESTRUCTION OF TRANSPLANTED ISLETS

Information

  • Research Project
  • 2790858
  • ApplicationId
    2790858
  • Core Project Number
    R43DK058027
  • Full Project Number
    1R43DK058027-01
  • Serial Number
    58027
  • FOA Number
  • Sub Project Id
  • Project Start Date
    9/30/1999 - 25 years ago
  • Project End Date
    8/31/2000 - 24 years ago
  • Program Officer Name
    HARMON, JOAN T.
  • Budget Start Date
    9/30/1999 - 25 years ago
  • Budget End Date
    8/31/2000 - 24 years ago
  • Fiscal Year
    1999
  • Support Year
    1
  • Suffix
  • Award Notice Date
    9/30/1999 - 25 years ago
Organizations

VACCINE: AUTO-IMMUNE DESTRUCTION OF TRANSPLANTED ISLETS

Anergen has proprietary technology for development of peptide vaccines against specific allele of MHC class II involved in autoimmune diseases, and has just completed a Phase II clinical trial for such a product in rheumatoid arthritis. We are testing a similar a similar vaccine, Diavax/TM, for prevention of primary insulin-dependent Type I diabetes (IDD) in a experimental animal model of IDD, the non-obese diabetic(NOD) mouse. This vaccine, which is a cyclic construct of a peptide from the third hyper-variable region of the murine IAg7 MHC class II beta chain, induces allele-specific antibodies (Ab), delays insulitis and prevents spontaneous development of IDD in our NOD colony for as long as we have measured (over 12 months). In this Phase I proposal, we will explore the possibility that the MHC vaccine-induced abrogation of autoreactive T cell destruction or beta cells can also prolong the life of engrafted islets in a transplant setting. We will determine whether anti- IAg7 Ab, either monoclonal or produced by vaccination with Diavax/TM, can extend the lie of syngeneic grafts (islets from young NOD engrafted into diabetic older NOD mice) as a preliminary indication that anti-MHC Ab can prolong graft survival in a setting not confounded by immune host-versus-graft rejection. In addition, if these syngeneic experiments are promising we will test he vaccine in a transplant setting more like that of humans, the allogeneic transplant of (NODxSJL) F1 hybrid mouse islets (expressing disparate MHC class I and II antigens of each parent) into diabetic NOD mice. Demonstration that vaccination prolongs graft viability and function will extend the usefulness of such an IDD vaccine, and will be a major advance in the treatment of IDD by islet transplant. PROPOSED COMMERCIAL APPLICATIONS: Type I diabetes affects one of every three hundred persons would wide. The national cost of diabetes in the U.S. is estimated to be over $92 billion yearly (JDF estimate). Anergen has patented a peptide vaccine of this type, DiavaX, which protects development of spontaneous diabetes in NOD mice. The aim of this study is to determine if the DiavaX vaccine can modulate the autoreactive T cells and prevent islet tissue destruction in early symptomatic NOD mice. If efficacy of the therapeutic vaccine can be demonstrated in late stage pre-diabetic NOD mice, Anergen, Inc., will initiate clinical development of the peptide vaccine against IDDM in humans.

IC Name
NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
  • Activity
    R43
  • Administering IC
    DK
  • Application Type
    1
  • Direct Cost Amount
  • Indirect Cost Amount
  • Total Cost
  • Sub Project Total Cost
  • ARRA Funded
  • CFDA Code
    847
  • Ed Inst. Type
  • Funding ICs
  • Funding Mechanism
  • Study Section
    ZRG2
  • Study Section Name
  • Organization Name
    CORIXA CORPORATION
  • Organization Department
  • Organization DUNS
  • Organization City
    Hamilton
  • Organization State
    MT
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    59840
  • Organization District
    UNITED STATES