Vaccination of mice with MUC1 cDNA suppresses the development of lung metastases

Vaccination of mice with MUC1 cDNA suppresses the development of lung metastases
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DOI:
10.1023/a:1021332932531
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发表时间:
2002-01-01
影响因子:
4
通讯作者:
Irimura, T
Irimura, T
中科院分区:
医学3区
文献类型:
--
作者:
Kamata, M;Denda-Nagai, K;Irimura, T

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用不同剂量的含有全长MUC 1 cDNA(22个串联重复序列)的纯化pCEP 4质粒DNA皮内免疫C57 BL/6小鼠。以每周间隔用MUC 1 DNA免疫三次的小鼠具有针对对应于MUC 1串联重复序列的合成肽的血清抗体。抗体滴度与质粒DNA剂量相关。在第三次免疫后,向小鼠静脉内注射5 × 105个已经用MUC 1 cDNA稳定转染的B16-F10黑素瘤细胞(F10-MUC 1-C8克隆细胞)。接种F10-MUC 1-C8细胞3周后,用MUC 1质粒DNA免疫的小鼠中肺转移结节的数量显著低于单独用载体DNA免疫的小鼠。因此,肺转移的抑制是抗原特异性的。在体内消耗淋巴细胞亚群的特异性抗体显示,自然杀伤细胞是主要的效应细胞负责抑制肺转移。CD 4(+)细胞和CD 8(+)细胞也起一定作用。
C57BL/6 mice were immunized intradermally with various doses of purified pCEP4 plasmid DNA containing full-length MUC1 cDNA (22 tandem repeats). Mice immunized with MUC1 DNA three times at weekly intervals had serum antibodies to a synthetic peptide corresponding to the tandem repeats of MUC1. The antibody titer correlated with the plasmid DNA dose. After the third immunization mice were injected intravenously with 5 x 10(5) B16-F10 melanoma cells that had been stably transfected with MUC1 cDNA (F10-MUC1-C8 clone cells). The number of lung metastatic nodules three weeks after inoculation of F10-MUC1-C8 cells was significantly lower in mice immunized with MUC1 plasmid DNA than in mice immunized with the vector DNA alone. Thus, the suppression of lung metastasis was antigen-specific. In vivo depletion of lymphocyte subpopulations by specific antibodies revealed that natural killer cells are the major effector cells responsible for the suppression of lung metastasis. CD4(+) cells and CD8(+) cells apparently played some roles too.