目的：探讨吉非替尼（gefitinib）联合靶向EGFR DNA疫苗对小鼠Lewis肺癌体内外的抑制作用。方法：用鸡EGFR与兔IgG Fc段异种融合DNA疫苗pVAX1/cEGFRrFc免疫小鼠制备抗血清，ELISA方法测定抗血清的效价。MTT法检测Lewis细胞的生长情况。建立Lewis肺癌鼠移植瘤模型，随机分为疫苗组、吉非替尼组、吉非替尼+疫苗组和对照组，观察各组小鼠肿瘤体积、重量及生存情况。结果：pVAX1/cEGFRrFc DNA疫苗免疫小鼠后抗EGFR血清效价为1∶1 000。与抗血清组或吉非替尼组相比，抗血清+吉非替尼组可显著抑制Lewis细胞的生长（P<0.05)。体内实验显示，吉非替尼+疫苗组小鼠移植瘤生长缓慢, 荷留小鼠生存率显著提高（P<0.01） 。结论：以EGFR为靶点的DNA疫苗和靶向药物吉非替尼之间具有协同性抗肿瘤作用，DNA疫苗主动免疫可以提高吉非替尼的疗效。

Objective:To observe the inhibitory effect of gefitinib combined with DNA vaccine targeting EGFR against implanted Lewis tumors in mice.Methods: Chicken EGFR L2 domain and rabbit IgG Fc domain fusion pVAX1/cEGFRrFc DNA vaccine was injected into mice and the titer of antiEGFR in serum was determined by ELISA. The growth of Lewis cells was measured by MTT. Lewis lung cancer mouse models were established and were randomly divided into vaccine, gefitinib, gefitinib+vaccine, and control groups. The tumor volume and weight and survival of mice were examined in different groups.Results:The titer of antiEGFR in mice vaccinated with pVAX1/cEGFRrFc plasmid was 1∶1 000. The proliferation of Lewis cells in antiEGFR combined with gefitinib was significantly inhibited compared with those in antiEGFR and gefitinib groups (P<0.05). In vivo results showed that the growth of implanted Lewis tumors in vaccine+gefitinib group was greatly inhibited, and the survival rate of Lewisbearing mice was significalty increased (P<001). Conclusion：DNA vaccine targeting EGFR has a synergistic effect with gefitinib in antitumor activity, and this DNA vaccine can increase the efficiency of gefitinib.

上海市科委重点基金资助项目（No.03DZ19236）；上海市肺科医院课题（No.200612）