[Studies on the enhancement of DC vaccine to mouse Lewis lung cancer by CpG oligonucleotides].
OBJECTIVE
To investigate whether CpG ODN can affect the antitumor responses of DC-tumor cell vaccine against Lewis lung cancer.


METHODS
CpG oligonucleotides 1826 (ODN 1826) were used to promote maturation of DCs in vitro. By fusing DCs with Lewis lung carcinoma L3-8 cells, DC-based tumor cell vaccines were developed. To determine the immune responses to the vaccines, T cell proliferation and cytotoxicity were done in vitro. Therapeutic and prophylactic immunization with DC vaccines were performed in C57BL/6 mice bearing Lewis lung carcinoma.


RESULTS
Bone marrow cells cultured in the presence of GM-CSF and IL-4 plus additional ODN 1862 appeared typical morphology of DCs. FACS analyses showed that the mean fluorescence index (MFI) of CD40 expression of DCs stimulated with and without CpG ODN was 24 and 11, respectively, and that of CD86 expression was 75 and 33, respectively. IL-12 secreted by DCs cultured with ODN 1826 was 10-fold as high as that without ODN 1826. Significant T-cell proliferation and T cell-mediated cytotoxicity against L3-8 was induced in vitro. Marked inhibition of tumor growth in L3-8 bearing mice was observed upon prophylactic and therapeutic immunizations with the vaccine.


CONCLUSIONS
CpG ODN can enhance the antitumor responses of DC vaccine by promoting DC maturation.
Du
Yu-Chen
YC
Division of Experimental Oncology, Key Laboratory of Biotherapy of Human Diseases, Sichuan University West China Hospital, Chengdu 610041, China.
Lin
Ping
P
Zhang
Jie
J
Lu
Yan-Rong
YR
Ning
Qi-Zhi
QZ
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000378:metabolism; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D018827:Carcinoma, Lewis Lung / Q000473:pathology / Q000517:prevention & control*; D002459:Cell Fusion; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D005260:Female; D018664:Interleukin-12 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D009368:Neoplasm Transplantation; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use
D015703:Antigens, CD; D051940:B7-2 Antigen; D019013:CD40 Antigens; C408982:CPG-oligonucleotide; D019496:Cancer Vaccines; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D018664:Interleukin-12