[The anti-tumor activity of GM-CSF-modified lung cancer cell vaccine and its synergism in combination with chemotherapy].
OBJECTIVE
To investigate the anti-tumor effects and mechanism of tumor vaccines and whether chemotherapeutic agents administered prior to immunotherapy could augment the efficacy of the vaccines.


METHODS
C57/BL mice inoculated with Lewis lung cancer cells were used as tumor models. Granulocyte-macrophage colony-stimulating factor (GM-CSF) gene modified LA795 and Lewis lung cancer cell lines were administered as allogeneic and autologous tumor vaccines, respectively. After Lewis cells (1 x 10(7)) inoculation, the mice received irradiated GM-CSF secreting cancer vaccine solely or in combination with carboplatin. The survival of the mice was observed. The cytotoxicity of spleen cells or purified CD8(+) cells was analyzed by lactate dehydrogenase (LDH) assay. Serum level of IL-4 and IFN-gamma was detected using ELISA method.


RESULTS
The cytotoxicity of the spleen cells or purified CD8(+) T cells against Lewis cells in the mice immunized with cancer cell vaccine was significantly increased, relative to that of the control, untreated group (P < 0.05). Serum level of Th1-type cytokine IFN-gamma was increased after vaccination, whereas Th2-type cytokine IL-4 showed no significant change. The GM-CSF secreting cancer cell vaccine had no significant influence on the survival of the mice with established heavy tumor burden. The combination of chemotherapy and cancer vaccine could statistically prolong the survival time; whereas any method itself had no significant effect.


CONCLUSIONS
The GM-CSF secreting cancer cell vaccine can induce immune responses. The chemotherapeutic agents may be beneficial to enhance the anti-tumor activity of cancer vaccine.
Jiang
Hong-Jing
HJ
Department of Thoracic Surgery, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China.
Ren
Xiu-Bao
XB
Li
Hui
H
Yu
Jin-Pu
JP
Wei
Feng
F
Ma
Ming-Quan
MQ
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000627:therapeutic use*; D016190:Carboplatin / Q000627:therapeutic use*; D018827:Carcinoma, Lewis Lung / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics* / Q000378:metabolism; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D014162:Transfection
D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016190:Carboplatin