title: CD8+ T cells targeting a single immunodominant epitope are sufficient for elimination of established SV40 T antigen-induced brain tumors.
abstract: Immunotherapy of established solid tumors is rarely achieved, and the mechanisms leading to success remain to be elucidated. We previously showed that extended control of advanced-stage autochthonous brain tumors is achieved following adoptive transfer of naive C57BL/6 splenocytes into sublethally irradiated line SV11 mice expressing the SV40 T Ag (T Ag) oncoprotein, and was associated with in vivo priming of CD8(+) T cells (T(CD8)) specific for the dominant epitope IV (T Ag residues 404-411). Using donor lymphocytes derived from mice that are tolerant to epitope IV or a newly characterized transgenic mouse line expressing an epitope IV-specific TCR, we show that epitope IV-specific T(CD8) are a necessary component of the donor pool and that purified naive epitope IV-specific T(CD8) are sufficient to promote complete and rapid regression of established tumors. While transfer of naive TCR-IV cells alone induced some initial tumor regression, increased survival of tumor-bearing mice required prior conditioning of the host with a sublethal dose of gamma irradiation and was associated with complete tumor eradication. Regression of established tumors was associated with rapid accumulation of TCR-IV T cells within the brain following initial priming against the endogenous T Ag in the peripheral lymphoid organs. Additionally, persistence of functional TCR-IV cells in both the brain and peripheral lymphoid organs was associated with long-term tumor-free survival. Finally, we show that production of IFN-gamma, but not perforin or TNF-alpha, by the donor lymphocytes is critical for control of autochthonous brain tumors.
authors.affiliation: Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Tatum
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Mylin
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Bender
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Fischer
authors.forename: Beth A
authors.initials: BA
authors.lastname: Vigliotti
authors.forename: M Judith
authors.initials: MJ
authors.lastname: Tevethia
authors.forename: Satvir S
authors.initials: SS
authors.lastname: Tevethia
authors.forename: Todd D
authors.initials: TD
authors.lastname: Schell