Autologous peptides eluted from acute myeloid leukemia cells can be used to generate specific antileukemic CD4 helper and CD8 cytotoxic T lymphocyte responses in vitro.
OBJECTIVE
The poor prognosis of acute myeloid leukemia (AML) treated with conventional chemotherapy justifies seeking additional immunotherapeutic approaches to eliminate minimal residual disease. Hence, we evaluated the feasibility of generating in vitro antileukemic immune responses, which would bypass the need for epitope identification and rely on antigen presentation by autologous dendritic cells.


METHODS
Naturally processed peptides were extracted by acid elution from circulating AML cells of six patients at diagnosis. Mature dendritic cells (mDC) were derived from autologous monocytes obtained when the patients were in complete remission, and were loaded with the pool of eluted peptides to stimulate autologous T lymphocytes in vitro.


RESULTS
We were able to induce in vitro antileukemic Th1 responses characterized by CD4(+) T-cell proliferation, significant interferon-gamma secretion by both CD4+ and CD8(+) T lymphocytes by recognition of autologous AML cells and generation of cytotoxic CD8(+) T lymphocytes.


CONCLUSIONS
These results demonstrate that naturally processed peptides eluted from AML cells and presented by differentiated autologous mDC could be immunogenic in vitro. Although more in vitro data will be needed to check the safety of such an approach, notably to rule out possible autoimmune adverse effects, these results lay the basis for a potentially effective antileukemic immunotherapy for high-risk AML patients with minimal residual disease.
Delluc
Stéphanie
S
Département d'Immunologie, Institut Cochin, Institut National de la Santé Et de la Recherche Médicale U 567, Centre National de Recherche Scientifique (CNRS) UMR 8104, Université René Descartes, Paris V.
Tourneur
Léa
L
Michallet
Anne-Sophie
AS
Boix
Charlotte
C
Varet
Bruno
B
Fradelizi
Didier
D
Guillet
Jean-Gérard
JG
Buzyn
Agnès
A
D000328:Adult; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood* / Q000276:immunology*; D008213:Lymphocyte Activation; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology / Q000302:isolation & purification; D010446:Peptide Fragments / Q000276:immunology / Q000302:isolation & purification; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology
D009363:Neoplasm Proteins; D010446:Peptide Fragments