Nonimmunogenic tumor cells may efficiently restimulate tumor antigen-specific cytotoxic T cells.

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 c...

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Main Authors: Kündig, T, Bachmann, M, Lefrancois, L, Puddington, L, Hengartner, H, Zinkernagel, R
Format: Journal article
Language:English
Published: 1993
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author Kündig, T
Bachmann, M
Lefrancois, L
Puddington, L
Hengartner, H
Zinkernagel, R
author_facet Kündig, T
Bachmann, M
Lefrancois, L
Puddington, L
Hengartner, H
Zinkernagel, R
author_sort Kündig, T
collection OXFORD
description 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.
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spelling oxford-uuid:16f612f1-7753-470d-8739-1b12c090cacb2022-03-26T10:34:18ZNonimmunogenic tumor cells may efficiently restimulate tumor antigen-specific cytotoxic T cells.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:16f612f1-7753-470d-8739-1b12c090cacbEnglishSymplectic Elements at Oxford1993Kündig, TBachmann, MLefrancois, LPuddington, LHengartner, HZinkernagel, RInduction 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.
spellingShingle Kündig, T
Bachmann, M
Lefrancois, L
Puddington, L
Hengartner, H
Zinkernagel, R
Nonimmunogenic tumor cells may efficiently restimulate tumor antigen-specific cytotoxic T cells.
title Nonimmunogenic tumor cells may efficiently restimulate tumor antigen-specific cytotoxic T cells.
title_full Nonimmunogenic tumor cells may efficiently restimulate tumor antigen-specific cytotoxic T cells.
title_fullStr Nonimmunogenic tumor cells may efficiently restimulate tumor antigen-specific cytotoxic T cells.
title_full_unstemmed Nonimmunogenic tumor cells may efficiently restimulate tumor antigen-specific cytotoxic T cells.
title_short Nonimmunogenic tumor cells may efficiently restimulate tumor antigen-specific cytotoxic T cells.
title_sort nonimmunogenic tumor cells may efficiently restimulate tumor antigen specific cytotoxic t cells
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AT puddingtonl nonimmunogenictumorcellsmayefficientlyrestimulatetumorantigenspecificcytotoxictcells
AT hengartnerh nonimmunogenictumorcellsmayefficientlyrestimulatetumorantigenspecificcytotoxictcells
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