Zhang Shuzi, Zhang Haihong, Shi Heliang, Yu Xianghui, Kong Wei, Li Wei
Vaccine Research Center, College of Life Science, Jilin University, Changchun, People's Republic of China.
Hum Immunol. 2008 Apr-May;69(4-5):250-8. doi: 10.1016/j.humimm.2008.02.006. Epub 2008 Apr 4.
Mucin 1 (MUC1) is a tumor-associated antigen that carries the important variable-number tandem repeat (VNTR) epitopes for inducing cytotoxic T lymphocytes. Such a property makes MUC1 VNTR potentially attractive for immunotherapy. This study explored the possibility of developing an efficient anti-tumor vaccine strategy using the specific antitumor immunity induced by the MUC1 VNTR DNA vaccine combined with the adjuvant effect of a plasmid expressing murine interleukin-2 (IL-2). The results showed that the MUC1 VNTR DNA vaccine successfully induced both humoral and cellular immune responses against MUC1 VNTR in mice. The effect could be obviously enhanced by increasing the number of tandem repeats, the number of immunizations, and by co-administration of the cytokine plasmid. The growth of MUC1-expressing (MUC1(+)) tumors was significantly inhibited in mice immunized with the MUC1 VNTR DNA vaccine combined with the IL-2 plasmid, both before and after tumor challenge. A much larger percentage of the immunized mice survived tumor challenge than the non-immunized mice. The combination of the MUC1 VNTR DNA vaccine and the IL-2 adjuvant plasmid provides an attractive alternative for prophylactic and therapeutic vaccinations against MUC1(+) tumors.
粘蛋白1（MUC1）是一种肿瘤相关抗原，携带可诱导细胞毒性T淋巴细胞的重要可变数目串联重复序列（VNTR）表位。这种特性使得MUC1 VNTR在免疫治疗方面具有潜在吸引力。本研究探讨了利用MUC1 VNTR DNA疫苗诱导的特异性抗肿瘤免疫与表达小鼠白细胞介素-2（IL-2）的质粒的佐剂作用，开发一种高效抗肿瘤疫苗策略的可能性。结果表明，MUC1 VNTR DNA疫苗成功诱导了小鼠针对MUC1 VNTR的体液免疫和细胞免疫反应。通过增加串联重复序列的数量、免疫次数以及联合使用细胞因子质粒，这种效果可得到明显增强。在用MUC1 VNTR DNA疫苗与IL-2质粒联合免疫的小鼠中，无论是在肿瘤攻击前还是攻击后，表达MUC1（MUC1(+)）的肿瘤生长均受到显著抑制。与未免疫的小鼠相比，免疫小鼠在肿瘤攻击后存活的比例要高得多。MUC1 VNTR DNA疫苗与IL-2佐剂质粒的联合为针对MUC1(+)肿瘤的预防性和治疗性疫苗接种提供了一种有吸引力的选择。
