Passive but not active CD8+ T cell-based immunotherapy interferes with liver tumor progression in a transgenic mouse model.
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.
Romieu
R
R
Laboratoire des Pathologies Infectieuses et Tumorales, Institut National de la Santé et de la Recherche Médicale U445, Paris, France. romieu@cochin.inserm.fr
Baratin
M
M
Kayibanda
M
M
Lacabanne
V
V
Ziol
M
M
Guillet
J G
JG
Viguier
M
M
D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000276:immunology; D000990:Antithrombin III / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000637:transplantation*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D004195:Disease Models, Animal; D018450:Disease Progression; D007108:Immune Tolerance / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology; D014611:Vaccination / Q000379:methods
D000952:Antigens, Polyomavirus Transforming; D010446:Peptide Fragments; D000990:Antithrombin III