Efficient monocyte-derived dendritic cell generation in patients with acute myeloid leukemia after chemotherapy treatment: application to active immunotherapy.
OBJECTIVE
While complete remission in acute myeloid leukemia (AML) can be achieved after chemotherapy (CT), relapses occur for the majority of patients, underlying the need to eliminate residual disease. Based on dendritic cell (DC) vaccination, the triggering of an immune response against residual leukemia cells after CT could maintain patients in remission. The aim of our study was to assess, for vaccine preparation, generation of monocyte-derived DCs in AML patients after CT.


METHODS
We evaluated efficiency of the production, yields, maturation, and functional properties of DCs from 22 AML patients at different CT stages compared to those from 15 healthy donors.


RESULTS
We demonstrated that monocyte-derived DC production is successful later than 3 weeks after the last CT cycle, whatever the CT was. Immature DCs demonstrated functional phagocytic activity. Mature DCs displayed migratory, T-cell stimulatory and Th1-activation capacities. Our results also suggest a favorable period from 20 to 60 days after CT for potent monocyte-derived DC production and immune activation.


CONCLUSIONS
In defining patient-sampling conditions, this preclinical study has direct implications for AML DC-based immunotherapy.
Royer
Pierre-Joseph
PJ
INSERM, U601, Nantes, France; Université de Nantes, Faculté de Médecine, Centre de Recherche en Oncologie, Nantes, France.
Bougras
Gwenola
G
Ebstein
Frederic
F
Leveque
Lucie
L
Tanguy-Royer
Severine
S
Simon
Thomas
T
Juge-Morineau
Nadine
N
Chevallier
Patrice
P
Harousseau
Jean-Luc
JL
Gregoire
Marc
M
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002454:Cell Differentiation; D017024:Chemotherapy, Adjuvant; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy*; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D054400:Receptors, CCR7 / Q000096:biosynthesis; D012074:Remission Induction; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome
C515370:CCR7 protein, human; D019496:Cancer Vaccines; D016207:Cytokines; D054400:Receptors, CCR7