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MUC-1 Tumor Antigen Agonist Epitopes for Enhancing T-cell Responses to Human Tumors

Posted Mar 26 2012 8:00pm

Description of Invention:
The MUC-1 tumor associated antigen has been shown to be overexpressed and/or underglycosylated in a wide range of human cancers. The C-terminus region of MUC-1 (MUC-1C) has been shown to be an oncogene and has been associated with a more aggressive phenotype in several different cancers.

Scientists at NIH have identified 7 new agonist epitopes of the MUC-1 tumor associated antigen. Compared to their native epitope counterparts, peptides reflecting these agonist epitopes have been shown to enhance the generation of human tumor cells, which in turn have a greater ability to kill human tumor cells endogenously expressing the native MUC-1 epitope. The agonist epitopes span both the VNTR region of MUC-1 and the C-terminus region. The epitopes encompass 2 major MHC alleles reflecting the majority of the population.

Along with the method of use, the technology encompasses the use of these agonist epitopes in peptide- and protein-based vaccines, with dendritic cells or other antigen presenting cells, or encoding sequences in DNA, viral, bacterial, yeast, or other types of vectors, or to stimulate T-cells in vitro for adoptive immunotherapy protocols.

Applications:
  • As a therapeutic vaccine to enhance patient’s immune responses to a range of human cancers
  • As a preventive vaccine for patients with preneoplastic conditions or a high risk of developing cancer
  • As a preventive vaccine for cancers
  • For in vitro stimulation of lymphocytes for adoptive transfer protocols for cancer


    • Advantages:
      • The agonist epitopes have been shown to be much more potent than their natural counterparts in activating human T-cells to MUC-1.
      • Compared to T-cells activated with the corresponding native epitopes, the T-cells activated by the agonist epitopes lyse tumor cells to a greater extent.
      • The technology can be used in a wide range of cancer vaccine platforms and in adoptive immunotherapy protocols.
      • The technology can be combined with existing vaccine platforms including those currently showing patient benefit, as well as with other therapeutic modalities.


      Development Status:
      • Early-stage
      • In vitro data available


      Inventors:
      Jeffrey Schlom (NCI)
      Kwong-Yok Tsang (NCI)


      Patent Status:
      HHS, Reference No. E-001-2012/0
      US, Application No. 61/582,723 filed 03 Jan 2012


      Related Technologies:
      PCT, Application No. PCT/US98/03693 filed 24 Feb 1998, Reference No. E-154-1998/0
      US, Patent No. 7,118,738, Issued 10 Oct 2006, Reference No. E-154-1998/0
      US, Patent No. 7,999,071, Issued 16 Aug 2011, Reference No. E-321-2003/0
      US, Application No. 13/176,341 filed 10 Dec 2004, Reference No. E-321-2003/0
      US, Application No. 60/529,329 filed 12 Dec 2003, Reference No. E-321-2003/0


      Collaborative Research Opportunity:
      The Laboratory of Tumor Immunology and Biology, National Cancer Institute, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize the use of MUC-1 tumor antigen agonist epitopes for the treatment or prevention of cancer. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov . Click here to view the NCI collaborative opportunity announcement.


      For Licensing Information Please Contact:
      Sabarni Chatterjee Ph.D.
      NIH Office of Technology Transfer
      6011 Executive Blvd. Suite 325,
      Rockville, MD 20852
      United States
      Email: chatterjeesa@mail.nih.gov
      Phone: 301-435-5587
      Fax: 301-402-0220


      Ref No: 2393

      Updated: 03/2012

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