MAGE-3抗原肽脉冲树突状细胞对小鼠胃癌移植瘤的免疫防护作用

目的观察MAGE3抗原肽脉冲的树突状细胞(DC/MAGE3)作为肿瘤疫苗抑制小鼠胃癌移植瘤生长的作用。方法检测了MAGE3抗原肽诱导出的细胞毒性T淋巴细胞(CTL)对小鼠前胃癌细胞株MFC细胞的杀伤活性。在免疫保护实验中先用DC/MAGE3(1×106个细胞/只)于小鼠皮下注射免疫两次,然后接种MFC细胞(5×105个细胞/只);在免疫治疗实验中先接种MFC细胞(5×105个细胞/只),然后在皮下注射DC/MAGE3(1×106个细胞/只)两次,并以感冒病毒核蛋白抗原肽脉冲的DC(DC/Nup)及空白DC作为对照,观察小鼠肿瘤的生长情况及其存活期并进行统计学处理。结果(1)MAGE3抗原肽诱导出的CTL细胞对MFC细胞有较高的杀伤活性;(2)在免疫保护实验和免疫治疗实验中DC/MAGE3可以明显地延缓肿瘤的生长,延长小鼠的生存时间(P<0.05)。结论MAGE3抗原肽脉冲的DC可通过加强抗原递呈激活肿瘤特异性CTL而具有明显的抗肿瘤活性。

Inhibitory effect of dendritic cells pulsed with MAGE-3 peptide on transplanted murine gastric cancer in mice

OBJECTIVE: To observe the inhibitory effect of MAGE-3 peptide pulsed DC on transplanted murine gastric cancer in 615 mice. METHODS: The CTL clones directed against MAGE-3 peptide were tested for the ability to lyse the gastric cancer cell line MFC which can express MAGE-3 antigen. In immunoprotection experiment, mice of the study group were immunized with MAGE-3 peptide pulsed DC (DC/MAGE-3) at the dosage of 1 x 10(6) on d0 and d7 by sc inoculation, mice of control groups were immunized with influenza virus peptide pulsed DC (DC/Nup) or unpulsed DC at the same dosage on days as the DC/MAGE-3 group. On d14, all the mice were challenged with sc injections of 5 x 10(5) MFC gastric cancer cells. In immunotherapy experiment, all the mice were sc injected 5 x 10(5) MFC gastric cancer cells on d0, and on d3, d10 mice of each groups were sc inoculated with DC/MAGE-3, DC/Nup or unpulsed DC at the dosage of 1 x 10(6) respectively. All mice were monitored closely with respect to tumor growth and survival times. RESULTS: The CTL clone induce by MAGE-3 peptide could lyse the MFC cells efficiently. Immunization of mice with DC pulsed with MAGE-3 generated partial protective immunity against MFC tumor, as well as significant inhibition of tumor growth in a 3-day tumor model. CONCLUSION: The tumor vaccine with DCs pulsed with MAGE-3 peptide possesses the ability to stimulate tumor specific CTL activity and to establish antitumor immunity when administered in vivo.