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Induction of immunity to a viral protein that had been transfected into a tumor cell line was studied. The nucleoprotein (NP) of vesicular stomatitis virus (VSV) was used as a model tumor-associated Ag after transfection into EL-4, and H-2b thymoma originating from C57BL/6 mice. The NP-transfected cell line (EL-4NP) was lysed by NP-specific CTL and was found to restimulate NP-specific CTL in vitro as efficiently as did VSV-infected macrophages. Despite both of these in vitro characteristics, C57BL/6 mice inoculated with EL-4NP did not mount a measurable NP-specific CTL response and developed a lethal tumor as rapidly as did mice given control EL-4. This lack of immunogenicity could not be explained by down-regulation of MHC class I molecules or by loss of NP; even EL-4NP cells metastasizing to the spleen kept their high restimulatory capacity and excellent target characteristics. However, once mice were immunized with VSV or with a vaccinia-VSV-NP recombinant virus they were protected against tumor growth of EL-4NP by CD8+ CTL but not by CD4+ T cells. Taken together, the failure of the tumor-associated Ag to induce a protective T cell response in vivo despite its excellent capacity to restimulate CTL in vitro may encourage adjuvant immunotherapy in cancer; even the effects of weakly immunizing tumor vaccines, e.g., recombinant viruses, may be efficiently amplified by tumor cells.


Journal article


Journal of immunology (Baltimore, Md. : 1950)

Publication Date





4450 - 4456


Institute of Experimental Immunology, University of Zürich, Switzerland.


T-Lymphocyte Subsets, CD4-Positive T-Lymphocytes, T-Lymphocytes, Cytotoxic, Tumor Cells, Cultured, Animals, Mice, Inbred C57BL, Mice, Thymoma, Neoplasms, Experimental, Nucleoproteins, Nucleocapsid Proteins, Viral Core Proteins, Antigens, Neoplasm, Antigens, Viral, Virus Replication, Vesicular stomatitis Indiana virus, In Vitro Techniques, CD8 Antigens