Studies on the Polyoma Virus Tumor-Specific Transplantation Antigen (Tsta)

Dalianis, Tina

doi:10.1016/s0065-230x(08)60468-6

Cited by 17 publications

(13 citation statements)

References 58 publications

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“…H5V-specific CTLs were readily detected in the MLTC of tumour-bearing mice, but only if low stimulator: responder cell ratios were used, while high numbers of H5V cells blocked responder cell proliferation and CTL generation. The observation of a CTL response in the H5V system contrasts with previous reports of unsuccessful attempts to generate tumour-specific CTL in polyoma tumour-bearing mice (Dalianis, 1990;Ljunggren et al, 1994). Indeed, the immunogenicity of the middle-T antigen was British Journal of Cancer (1998) 77(4), [656][657][658][659][660][661][662] IL-12 treatment of haemangiosarcomas 661 only demonstrated after immunization with middle-T peptide fragments, whereas the development of tumour-specific CTL in polyoma tumour-bearing mice was not directly shown (Reinholddson-Ljunggren et al, 1992).…”

Section: Discussioncontrasting

confidence: 97%

Therapeutic effect of interleukin 12 on mouse haemangiosarcomas is not associated with an increased anti-tumour cytotoxic T-lymphocyte activity

Vízler

Rosato²,

Calderazzo³

et al. 1998

Br J Cancer

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Summary In syngeneic mice, the H5V polyoma middle-T oncogene-transformed endothelioma cell line induces Kaposi's sarcoma-like cavernous haemangiomas that regress transiently, probably because of an anti-tumour immune response, but eventually grow progressively and kill the host. To evaluate the generation of tumour-specific cytotoxic T lymphocytes (CTLs), spleen cells of tumour-bearing mice were restimulated with irradiated H5V cells in mixed leucocyte-tumour cell cultures. Tumour-specific CTLs were demonstrable only when low numbers of H5V stimulator cells were used (<1 H5V cell per 50 splenocytes). We found that H5V cells secrete immunosuppressive mediators because CTL generation was blocked when H5V cells culture supernatants were added to allogeneic mixed leucocyte cultures. As numerous tumour-derived immunosuppressive mediators may interfere with interleukin 12 (IL-12) production, we tested whether IL-12 treatment of the tumour-bearing mice would augment their immune response and thus suppress tumour growth. Indeed, IL-12 inhibited tumour growth and prevented mortality, but did not increase anti-H5V CTL generation either in vitro or in vivo. Moreover, the anti-tumour activity in IL-12-treated mice was abrogated by anti-interferon (IFN)-y monoclonal antibody (MAb) co-administration. These results strongly suggest that the antitumour effect of IL-12 is principally mediated by IFN-y release that in turn blocks H5V cell proliferation and induces the release of factors that suppress angiogenesis.

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Section: Discussioncontrasting

confidence: 97%

Therapeutic effect of interleukin 12 on mouse haemangiosarcomas is not associated with an increased anti-tumour cytotoxic T-lymphocyte activity

Vízler

Rosato²,

Calderazzo³

et al. 1998

Br J Cancer

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“…Attempts have been made to elicit tumor immunity through inoculation of purified antigens or tumor lysates (1)(2)(3)(4)(5)(6)(7) or anti-idiotypic antibodies directed against tumor-associated antigens (8)(9)(10). Such approaches have met with only limited success, and we have used instead live recombinant vaccinia viruses expressing tumor antigens to immunize against tumor cells.…”

mentioning

confidence: 99%

Vaccination against tumor cells expressing breast cancer epithelial tumor antigen.

Hareuveni

Gautier

Kiény

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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Ninety-one percent of breast tumors aberrantly express an epithelial tumor antigen (ETA) identified by monoclonal antibody H23. Vaccinia virus recombinants expressing tumor antigens have considerable promise in the active immunotherapy of cancer, and we have evaluated the potential of vaccinia recombinants expressing the secreted (S) and cell-associated (transmembrane, T) forms of H23 ETA to elicit immunity to tumor cells expressing ETA. Tumorigenic ras-transformed Fischer rat fibroblast lines FR-S and FR-T, expressing the S or T form of H23 ETA, respectively, were constructed for use in challenge experiments. Expression of H23 ETA in these lines was confirmed by Western blotting and immunofluorescence. When challenged by subcutaneous seeding of tumor cells, 97% (FR-S) and 91% (FR-T) of syngeneic Fischer rats rapidly developed tumors that failed to regress. Vaccination with recombinant vaccinia virus expressing ETA-T prior to challenge prevented tumor development in 82% of animals seeded with FR-T cells but in only 61% of animals seeded with FR-S. The vaccinia recombinant expressing the S form was a less effective immunogen, and vaccination protected only 29-30% of animals from developing tumors upon challenge with either FR-S or -T cells. The increased immunogenicity of the recombinant expressing ETA-T was reflected in elevated levels of ETA-reactive antibody in vaccinated animals, confirming that secreted antigens expressed from vaccinia virus are less effective immunogens than their membrane-associated counterparts.

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“…Effective manipulation of the T-cell response against tumors requires thorough understanding of the nature of the antigens recognized. CD8+ CTL react predominantly with internally derived antigens expressed on the cell surface as small peptides in the antigen-binding groove of MHC-class-I molecules (Townsend and Bodmer, 1989).The nature of tumor-specific transplantation antigens (TSTA) of virus-induced tumors is likely to represent short peptides derived from sequences of the viral proteins (Dalianis, 1990;Melief, 1992). Synthetic peptides derived from aa sequences of the LT, MT and ST antigens of the py virus have been reported to immunize against py-virus-induced murine tumors (Ramqvist et a/., 1989;Reinholdsson-Ljunggren et a/., 1992;Reinholdsson-Ljunggren and Dalianis, 1992).…”

mentioning

confidence: 99%

Identification of H‐2K^b‐, D^b‐ and D^d‐binding peptides derived from amino acid sequences of polyoma virus T antigens

Reinholdsson-Ljunggren

Franksson

Dalianis

et al. 1993

Intl Journal of Cancer

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Viral and tumor antigens are presented to cytotoxic T cells (CTL) in the form of short peptides. The peptide antigen is transported to the cell surface in conjunction with molecules encoded by the major histocompatibility complex (MHC). Different methods have recently been described for the analysis of the MHC-class-I binding ability of synthetic peptides. Here, we describe a protocol, based on intact RMA-S cells cultured at 26 degrees C in the presence of synthetic peptides, which gives an allele-specific peptide binding pattern with high resolution. This allowed an analysis of the H-2Kb-, Db- and Dd-binding capacity of a panel of synthetic peptides with amino acid (aa) sequences derived from polyoma (py) virus large-, middle- and small-T (LT, MT and ST) antigens, previously used in immunization experiments against py-virus-induced tumors. Eight single aa mutants and a deletion mutant of one peptide with an ability to bind both to H-2Kb and to Db were also analyzed. We foresee that the present protocol, or variants thereof, may serve as a simple and rapid assay for the systematic screening of the class-I binding ability of large sets of synthetic peptides in vitro. Such analysis may facilitate the search for viral or tumor peptide epitopes that are recognized by CTL.

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Studies on the Polyoma Virus Tumor-Specific Transplantation Antigen (Tsta)

Cited by 17 publications

References 58 publications

Therapeutic effect of interleukin 12 on mouse haemangiosarcomas is not associated with an increased anti-tumour cytotoxic T-lymphocyte activity

Therapeutic effect of interleukin 12 on mouse haemangiosarcomas is not associated with an increased anti-tumour cytotoxic T-lymphocyte activity

Vaccination against tumor cells expressing breast cancer epithelial tumor antigen.

Identification of H‐2K^b‐, D^b‐ and D^d‐binding peptides derived from amino acid sequences of polyoma virus T antigens

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Studies on the Polyoma Virus Tumor-Specific Transplantation Antigen (Tsta)

Cited by 17 publications

References 58 publications

Therapeutic effect of interleukin 12 on mouse haemangiosarcomas is not associated with an increased anti-tumour cytotoxic T-lymphocyte activity

Therapeutic effect of interleukin 12 on mouse haemangiosarcomas is not associated with an increased anti-tumour cytotoxic T-lymphocyte activity

Vaccination against tumor cells expressing breast cancer epithelial tumor antigen.

Identification of H‐2Kb‐, Db‐ and Dd‐binding peptides derived from amino acid sequences of polyoma virus T antigens

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Identification of H‐2K^b‐, D^b‐ and D^d‐binding peptides derived from amino acid sequences of polyoma virus T antigens