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

Details

Serval ID
serval:BIB_5A085EFD49F0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Ex vivo characterization of multiepitopic tumor-specific CD8 T cells in patients with chronic myeloid leukemia: implications for vaccine development and adoptive cellular immunotherapy
Journal
J Immunol
Author(s)
Gannage M., Abel M., Michallet A. S., Delluc S., Lambert M., Giraudier S., Kratzer R., Niedermann G., Saveanu L., Guilhot F., Camoin L., Varet B., Buzyn A., Caillat-Zucman S.
ISSN
0022-1767 (Print)
ISSN-L
0022-1767
Publication state
Published
Issued date
2005
Volume
174
Number
12
Pages
8210-8
Language
english
Notes
Gannage, Monique
Abel, Michal
Michallet, Anne-Sophie
Delluc, Stephanie
Lambert, Marion
Giraudier, Stephane
Kratzer, Roland
Niedermann, Gabriele
Saveanu, Loredana
Guilhot, Francois
Camoin, Luc
Varet, Bruno
Buzyn, Agnes
Caillat-Zucman, Sophie
eng
Research Support, Non-U.S. Gov't
J Immunol. 2005 Jun 15;174(12):8210-8. doi: 10.4049/jimmunol.174.12.8210.
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.
Keywords
Antigens, Neoplasm/immunology/metabolism, CD8-Positive T-Lymphocytes/*immunology/metabolism/pathology, Cancer Vaccines/*immunology, DNA-Binding Proteins/immunology/metabolism, Epitopes, T-Lymphocyte/*immunology/metabolism, Fusion Proteins, bcr-abl/immunology/metabolism, HLA-A2 Antigen/metabolism, Humans, Immunologic Memory, Immunophenotyping, *Immunotherapy, Adoptive/methods, Interferon-gamma/biosynthesis, Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*immunology/pathology/*therapy, Lymphocyte Count, Myeloblastin, Peptide Fragments/metabolism, Protein Binding/immunology, Serine Endopeptidases/immunology/metabolism, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Telomerase/immunology/metabolism, WT1 Proteins/immunology/metabolism
Pubmed
Create date
10/03/2022 11:43
Last modification date
11/03/2022 7:33
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