AML-loaded DC generate Th1-type cellular immune responses in vitro.
BACKGROUND
The generation of AML-specific T-lymphocyte responses by leukemia-derived DC has been documented by multiple investigators and is being pursued clinically. An obstacle to widespread use of this strategy is that it has not been possible to generate leukemic DC from all patients, and an alternative approach is needed if the majority of leukemia patients are to receive therapeutic vaccination in conjunction with other treatment protocols.


METHODS
In the present study, we generated DC from CD14-selected monocytes isolated from healthy donor PBPC and loaded them with a total cell lysate from AML patient blasts.


RESULTS
Immature in vitro-derived DC exhibited robust phagocytic activity, and mature DC demonstrated high expression of CD80, CD83, CD86 and the chemokine receptor CCR7, important for DC migration to local lymph nodes. Mature, Ag-loaded DC were used as APC for leukemia-specific cytotoxic T-lymphocyte (CTL) induction and demonstrated cytotoxic activity against leukemic targets. CTL lysis was Ag-specific, with killing of both allogeneic leukemic blasts and autologous DC loaded with allogeneic AML lysate. HLA-matched controls were not lysed in our system.


CONCLUSIONS
These data support further research into the use of this strategy as an alternative approach to leukemia-derived DC vaccination.
Xing
D
D
The University of Texas MD Anderson Cancer Center, Department of Blood and Marrow Transplantation, Houston, Texas 77030, USA.
Decker
W K
WK
Li
S
S
Robinson
S N
SN
Yang
H
H
Segal
H
H
O'Connor
S
S
Yao
X
X
Komanduri
K V
KV
McMannis
J D
JD
Jones
R B
RB
de Lima
M
M
Champlin
R E
RE
Shpall
E J
EJ
D000208:Acute Disease; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000502:physiology; D015703:Antigens, CD / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D007938:Leukemia / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016014:Linear Models; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D019707:Receptors, Chemokine / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D015703:Antigens, CD; D007375:Interleukin-1; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma