Using virally expressed melanoma cDNA libraries to identify tumor-associated antigens that cure melanoma.

Multiple intravenous injections of a cDNA library, derived from human melanoma cell lines and expressed using the highly immunogenic vector vesicular stomatitis virus (VSV), cured mice with established melanoma tumors. Successful tumor eradication was associated with the ability of mouse lymphoid cells to mount a tumor-specific CD4(+) interleukin (IL)-17 recall response in vitro. We used this characteristic IL-17 response to screen the VSV-cDNA library and identified three different VSV-cDNA virus clones that, when used in combination but not alone, achieved the same efficacy against tumors as the complete parental virus library. VSV-expressed cDNA libraries can therefore be used to identify tumor rejection antigens that can cooperate to induce anti-tumor responses. This technology should be applicable to antigen discovery for other cancers, as well as for other diseases in which immune reactivity against more than one target antigen contributes to disease pathology.
AuthorsJose Pulido, Timothy Kottke, Jill Thompson, Feorillo Galivo, Phonphimon Wongthida, Rosa Maria Diaz, Diana Rommelfanger, Elizabeth Ilett, Larry Pease, Hardev Pandha, Kevin Harrington, Peter Selby, Alan Melcher, Richard Vile
JournalNature biotechnology (Nat Biotechnol) Vol. 30 Issue 4 Pg. 337-43 (Apr 2012) ISSN: 1546-1696 [Electronic] United States
PMID22426030 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, Neoplasm
  • Epitopes, T-Lymphocyte
  • HSP70 Heat-Shock Proteins
  • Interleukin-17
  • Animals
  • Antigens, Neoplasm (immunology, isolation & purification)
  • CD4-Positive T-Lymphocytes (immunology)
  • Cell Line, Tumor
  • Epitopes, T-Lymphocyte (immunology)
  • Gene Library
  • Genetic Vectors
  • HSP70 Heat-Shock Proteins (metabolism)
  • Humans
  • Interleukin-17 (immunology)
  • Lymphocytes (immunology)
  • Melanoma (genetics, immunology, therapy)
  • Melanoma, Experimental
  • Mice
  • Neoplasms, Experimental (immunology, therapy)
  • Vesiculovirus

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