Passive but not active CD8+ T cell-based immunotherapy interferes with liver tumor progression in a transgenic mouse model.

Abstract

To evaluate tumor immunotherapies, we used transgenic mice that harbor a progressive liver tumor associated with the expression of the SV40 large tumor T oncoprotein (SV40-T). To induce "self" tumor Ag-specific CD8+ T cells, mice were injected with an immunodominant SV40-T CTL epitope mixed with a heterologous helper peptide. Despite repeated injections, this vaccine failed to raise a tumor-specific CD8+ T cell response that was efficient enough to counteract tumors. Although coimmunization with SV40-T CTL epitope and heterologous helper peptide efficiently recruited the respective Th cells, only low-avidity SV40-T-specific CD8+ T cells were activated. Furthermore, major alterations in SV40-T-specific B and Th cell responses were characterized. In contrast, transfers of higher-avidity CTLs specific for the same SV40-T epitope were effective in counteracting tumors. These results suggest that passive therapies targeted to self tumor Ag may be more suitable than active immunization in the treatment of spontaneous tumors.

• Authors: R Romieu, M Baratin, M Kayibanda, V Lacabanne, M Ziol, J G Guillet, M Viguier
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 161 Issue 10 Pg. 5133-7 (Nov 15 1998) ISSN: 0022-1767 [Print] United States
• PMID: 9820481 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Polyomavirus Transforming
• Peptide Fragments
• Antithrombin III

Topics

• Adoptive Transfer (methods)
• Animals
• Antigens, Polyomavirus Transforming (genetics, immunology)
• Antithrombin III (genetics)
• CD8-Positive T-Lymphocytes (transplantation)
• Carcinoma, Hepatocellular (genetics, immunology, prevention & control)
• Disease Models, Animal
• Disease Progression
• Immune Tolerance (genetics)
• Liver Neoplasms (genetics, immunology, prevention & control)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Inbred DBA
• Mice, Transgenic
• Peptide Fragments (immunology)
• Vaccination (methods)