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. 2005 Jun 15;174(12):8210-8.
doi: 10.4049/jimmunol.174.12.8210.

Ex vivo characterization of multiepitopic tumor-specific CD8 T cells in patients with chronic myeloid leukemia: implications for vaccine development and adoptive cellular immunotherapy

Monique Gannagé  1 , Michal Abel, Anne-Sophie Michallet, Stéphanie Delluc, Marion Lambert, Stéphane Giraudier, Roland Kratzer, Gabriele Niedermann, Loredana Saveanu, François Guilhot, Luc Camoin, Bruno Varet, Agnès Buzyn, Sophie Caillat-Zucman
Affiliations

Ex vivo characterization of multiepitopic tumor-specific CD8 T cells in patients with chronic myeloid leukemia: implications for vaccine development and adoptive cellular immunotherapy

Monique Gannagé et al. J Immunol. .

Abstract

Identification of tumor-associated Ags is a prerequisite for vaccine-based and adoptive immune therapies. Some tumor-associated Ags elicit specific CD8 T cells in patients with chronic myeloid leukemia (CML). Here, we characterized ex vivo responses of CD8 T cells from CML patients to extrajunction bcr-abl peptides and telomerase 540-548 hTert, PR1, and WT1 peptides. CML-specific CD8 T cells were present in most treated patients and were usually multiepitopic: WT1, hTert, PR1, and bcr74 tetramer(+) cells were detected in 85, 82, 67, and 61% of patients, respectively. The breadth and magnitude of these responses did not differ significantly according to treatment or disease status. CML-specific tetramer(+) CD8 T cells had a predominantly memory phenotype, an intermediate perforin content, and low intracellular IFN-gamma accumulation in the presence of the relevant peptide. However, in short-term culture with HLA-matched leukemia cells, the patients' memory T cells were specifically reactivated to become IFN-gamma-producing effector cells, suggesting that CD8 T cell precursors with lytic potential are present in vivo and can be activated by appropriate stimulation. In conclusion, this study shows that multiepitopic tumor-specific CD8 T cell responses occur naturally in most CML patients, opening the way to new strategies for enhancing anti-CML immunity, in particular in patients with minimal residual disease.

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