佐剂增强的肿瘤细胞裂解物疫苗抗小鼠H22肝癌作用

H22 tumor cell lysate plus adjuvants can effectively induce anti-tumor immunity

以鼠源肝癌H22全细胞裂解物为抗原,通过化学偶联白喉毒素(DT)和串联重复的T辅助表位mH-SP70407-426肽段,混合OK432(链球菌A群)制成肿瘤全细胞疫苗H22-DT-M2-OK432(HDTMOK)。治疗性免疫结果显示,疫苗激发的免疫应答对H22肿瘤起到了有效的抑制作用。为进一步提高该疫苗的抗肿瘤效果,用偶联的疫苗制备免疫刺激复合物(ISCOM),并验证其抑瘤效果。治疗性免疫结果显示,与PBS组相比,ISCOM疫苗组平均瘤重和瘤体积显著降低(P<0.01),同时有效地抑制了小鼠皮内肿瘤模型中的血管新生(P<0.01);ELISA法从血清中检测到高滴度的抗体。且与HDTMOK疫苗相比,ISCOM疫苗抑瘤作用提升显著(P<0.05)。HDTMOK能有效抑制小鼠肝癌实体瘤生长,佐剂配伍后的疫苗对H22的抑制更为显著,能够有效提升肿瘤全细胞疫苗的抗肿瘤能力。

Whole cell lysate of mouse hepatoma （H22） was prepared and processed to the whole tumor cell vaccine H22-DT-M2-OK432 （ abbreviated as HDTMOK） by chemical coupling a mixture of DT and microbial HSP70 peptide epitope 407-426 and addition of OK432 as antigen. According to the results of therapeutic immune, the immune response stimulated by HDTMOK had effectively in- hibited the growth of H22. Compared with that of the PBS group, the average weight and size of the tumor had both significantly reduced （P 〈 0. 05 ）. In order to enhance the anti-tumor effect of the vaccines, immunostimulating complex （ISCOM） were prepared on the basis of HDTMOK. Therapeutic immune results showed that the mean weight and size of excised tumors significantly reduced compared with that of the PBS group （ P 〈 0.01 ）. ISCOM also effectively retarded the angiogenesis of intradermal tumor model （ P 〈 0. 01 ）. Meanwhile, the anti-tumor effect was also strengthened in comparison with HDTMOK （P 〈 0. 05）.