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Chemokine-Tumor Antigen Fusion Proteins as Cancer Vaccines

Posted Nov 01 2010 8:00pm

Description of Invention:
Available for licensing is a tumor vaccine construct comprising a chemoattractant (such as human chemokines CCL7 and CCL20) fused to a tumor antigen (including human mucin-1, a transmembrane protein that is aberrantly expressed in cancer; or single chain antibody expressed by B cell malignancy, or melanoma antigen gp100 expressed in human melanomas). The majority of tumor antigens are believed to be poorly immunogenic because they represent oncogene gene products or other cellular genes which are normally present in the host. As a result, poor immunogenicity has been a major obstacle to successful immunotherapy with tumor vaccines. Administration of this fusion chemokine and tumor antigen protein, or a nucleic acid encoding this fusion protein, elicits a tumor specific cellular and humoral immune response thereby providing a potent cancer vaccine.

Applications:
Cancer immunotherapy

Development Status:
Proof of the concept and pre-clinical development have been successfully completed.

Inventors:
Larry W Kwak (NCI)
Arya Biragyn (NCI)


Patent Status:
HHS, Reference No. E-107-1998/0
US, , Patent No. 6,562,347, Issued 13 May 2003


Relevant Publication:
  1. Coscia M, Biragyn A. Cancer immunotherapy with chemoattractant peptides. Semin Cancer Biol. 2004 Jun;14(3):209-218. [ PubMed: 15246057 ]
  2. Biragyn A, Belyakov IM, Chow YH, Dimitrov DS, Berzofsky JA, Kwak LW. DNA vaccines encoding human immunodeficiency virus-1 glycoprotein 120 fusions with proinflammatory chemoattractants induce systemic and mucosal immune responses. Blood. 2002 Aug 15;100(4):1153-1159. [ PubMed: 12149191 ]
  3. Schiavo R, Baatar D, Olkhanud P, Indig FE, Restifo N, Taub D, Biragyn A. Chemokine receptor targeting efficiently directs antigens to MHC class I pathways and elicits antigen-specific CD8+ T-cell responses. Blood. 2006 Jun 15;107(12):4597-4605. [ PubMed: 16514063 ]
  4. Biragyn A, Ruffini PA, Coscia M, Harvey LK, Neelapu SS, Baskar S, Wang JM, Kwak LW. Chemokine receptor-mediated delivery directs self-tumor antigen efficiently into the class II processing pathway in vitro and induces protective immunity in vivo. Blood. 2004 Oct 1;104(7):1961-1969. [ PubMed: 15191951 ]
  5. Qin H, Nehete PN, He H, Nehete B, Buchl S, Cha SC, Sastry JK, Kwak LW. Prime-boost vaccination using chemokine-fused gp120 DNA and HIV envelope peptides activates both immediate and long-term memory cellular responses in rhesus macaques. J Biomed Biotechnol. 2010;2010:860160. [ PubMed: 20454526 ]
  6. Qin H, Cha SC, Neelapu SS, Lou Y, Wei J, Liu YJ, Kwak LW. Vaccine site inflammation potentiates idiotype DNA vaccine-induced therapeutic T cell-, and not B cell-, dependent antilymphoma immunity. Blood. 2009 Nov 5;114(19):4142-4149. [ PubMed: 19749091 ]
  7. Singh A, Nie H, Ghosn B, Qin H, Kwak LW, Roy K. Efficient modulation of T-cell response by dual-mode, single-carrier delivery of cytokine-targeted siRNA and DNA vaccine to antigen-presenting cells. Mol Ther. 2008 Dec;16(12):2011-2021. [ PubMed: 18813280 ]


Licensing Status:
Available for licensing.

Collaborative Research Opportunity:
The National Institute on Aging, Laboratory of Immunology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize cancer vaccines that target skin antigen-resenting cells. Please contact Nicole Guyton at 301-435-3101 or guytonn@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.


Portfolios:
Cancer
Cancer - Therapeutics
Infectious Diseases
Infectious Diseases - Vaccines



For Licensing Information Please Contact:
Patrick McCue Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: McCuepat@mail.nih.gov
Phone: 301-496-7057
Fax: 301-402-0220


Ref No: 1251

Updated: 11/2010

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