Induction of specific CTL by MAGE-3/CEA peptide-pulsed dendritic cells from HLA-A2/A24(+) gastrointestinal cancer patients.
OBJECTIVE
In this study, we aimed to investigate whether MAGE3/CEA peptide-pulsed dendritic cells could induce specific cytotoxic T lymphocytes (CTL).


METHODS
In this pilot study, we selected 25 patients expressing MAGE-3-HLA-A2/A24 or CEA-HLA-A24. Patients' dendritic cells (DCs) were expanded in vitro in the presence of recombined-human granular macrophage colony stimulating factor (rhGM-CSF) and recombined-human interleukin 4 (rhIL-4), pulsed with MAGE-3/CEA (HLA-A2/A24) peptide. The cytolytic cells' activity, induced by peptide-pulsed DCs and unpurified T cells as effector cells, and with Mel526, 803, Raji, and K562 as target cells, were measured using LDH-releasing assay.


RESULTS
DCs were obtained by in vitro expansion in all cases although DC harvest rates varied among different patients (7.1+/-3.2%). Compared with T-IL-2 (IL-2-induced T cells), T-DC-P - which resulted from T-IL-2 co-cultured with DCs pulsed by MAGE3 or CEA peptides - exhibited an increase in cytolytic activity against Mel526 (expressing MAGE-3-HLA-A2) and 803 (expressing CEA-HLA-A24) cell lines by about 25-30% ( P<0.01). In contrast, there was no significant difference between the activity against Raji and K562 cells, which are negative for both peptides.


CONCLUSIONS
This study showed that combined usage of rhGM-CSF and rhIL-4 in vitro could expand DCs, and that the DCs pulsed with specific peptides could induce MAGE- and CEA-specific CTL responses. The DC-based vaccine may provide an important method for the immunological treatment of gastrointestinal cancers.
Hao
Xishan
X
Department of Immunology, Tianjin Cancer Institute & Hospital, Tianjin Medical University, Huanhu Xi Road, Tianjin 300060, China. rwziyi@yahoo.com
Shao
Ying
Y
Ren
Xiubao
X
Liu
Hong
H
Xu
Qi
Q
Li
Hui
H
Zhang
Peng
P
An
Xiumei
X
Ren
Baozhu
B
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology*; D059871:HLA-A24 Antigen; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000951:Antigens, Neoplasm; D002272:Carcinoembryonic Antigen; D015234:HLA-A Antigens; D015789:HLA-A2 Antigen; D059871:HLA-A24 Antigen; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D010455:Peptides