| Objective: Gastric carcinoma is one of the most common malignant tumors in the world. With the traditional treatments to this disease, which are radical operation, chemotherapy and radiotherapy, many patients still have to face a poor prognosis. Cancer immunotherapy is one of the treatments with new hopes, in which dendritic cell (DCs) tumor vaccine is broadly researched in laboratories and widely tested in clinical trails. Even though, there are few reports on gastric cancer treated with dendritic tumor vaccine. We had previously reported that DCs pulsed with gastric tumor antigen can induce powerful anti-cancer immunity to kill cancer cells efficiently in vitro. In present study, we aim to investigate the in vivo anti-cancer effects of DCs tumor vaccine in nude mice and try to explain the mechanism of this effect. We also want to explore the preparation, identification and application of the DCs vaccine.Methods: Soluble tumor antigen was prepared by four freeze-thaw cycles of gastric tumor cell line SCG7901. Anti-cancer DCs vaccine was acquired by co-incubation of tumor antigen to the mouse bone marrow-derived dendritic cells generated with granulocyte/macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4). This vaccine was used to induce cytotoxic T lymphocytes out of splenocytes, which was gastric cancer specific and was applied to the subcutaneous nude mice tumor model. The anti-cancer effects were evaluate by detecting the apoptosis and proliferation of tumor cell, serum vascular endothelia growth factor (VEGF) level and tissue pathologic changesof the tumor model.Results: (1)DCs generated from mouse bone marrow by 7 days culture with GM-CSF and IL-4 showed typical shapes under light microscope and scanning electronic microscope. And CD1a(84.7%), CD11c(82.3%), CD40(54.8%) and CD80(74.3%) were highly expressed on the surface of this kind of DCs. (2) The gastric tumor specific DCs expressed higher CD80(90.4%)than DCs that did not pulsed with the antigen. This vaccine showed potent ability to prime antigen specific cellular immunity in mouse after one single infuse 7 days before, and the infuse route greatly affected the results of the priming. Venous route may be favorable, and peritoneal route may be another good choice.(3) Tumor growth was inhibited and the tumor size in treat group was 1.41±0.37cm3, which was extensively smaller than the size of control group(2.36±0.32cm3)(P<0.01). The tumor cells proliferation index in treat group(27.8±7.5) is significantly down-regulated than that in the control group(38.7±5.7)(P<0.01). Detected by Annexin-V/PI double labeling flow-cytometry, tumor cell apoptosis rate of treat group (56.2±14.1%)was promoted extensively than that of the control group(16.8±7.5%)(P<0.01). The serum VEGF level of treat group was also found to be significantly lower than that of the control group(240±173pg/ml to 790±221pg/ml)(P<0.01). And more infiltrated lymphocytes and apoptotic tumor cells were founded in the tumor tissue of the treat group compared with the control group(P<0.01). Conclusion: DCs gastric cancer vaccine is very efficacious, which inhibit cancer growth by promoting apoptosis and down regulating the proliferation, and subsequently reduce the serum VEGF level. These results indicate that DCs vaccine may be a useful tool for the clinical immunotherapy of gastric cancer.
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