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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。
Using murine hepatocellular carcinoma H22 whole cell lysate as an antigen, whole-cell tumor cells were prepared by chemically conjugating diphtheria toxin (DT) and tandem repeat T helper epitope mH-SP70407-426 peptide and mixing OK432 (Streptococcus group A) Vaccine H22-DT-M2-OK432 (HDTMOK). Therapeutic immunization results showed that the vaccine-stimulated immune response effectively inhibited H22 tumors. To further improve the anti-tumor effect of this vaccine, immunostimulatory complex (ISCOM) was prepared with the conjugate vaccine and the anti-tumor effect was verified. The therapeutic immunization results showed that the mean tumor weight and tumor volume of ISCOM vaccine group were significantly lower than those of PBS group (P <0.01), and angiogenesis was inhibited in mice intradermal tumor model (P <0.01). High-titer antibody was detected by ELISA from serum. Compared with the HDTMOK vaccine, ISCOM vaccine showed significant anti-tumor effect (P <0.05). HDTMOK can effectively inhibit the growth of solid tumor in mice with hepatocellular carcinoma. The vaccine with adjuvant is more effective in inhibiting H22 and can effectively improve the anti-tumor ability of the whole cell vaccine of tumor.