DNA vaccination against rat Her-2/neu p185 more effectively inhibits carcinogenesis than transplantable carcinomas in transgenic BALB/c mice
DNA vaccination against rat Her-2/neu p185 more effectively inhibits carcinogenesis than transplantable carcinomas in transgenic BALB/c mice
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DOI：
10.4049/jimmunol.165.9.5133
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发表时间：
2000-11-01
影响因子：
4.4
通讯作者：
Forni, G
中科院分区：
文献类型：
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作者：
Rovero, S;Amici, A;Forni, G
评估了用编码转化大鼠Her-2/neu癌基因(r-p185)产物的胞外和跨膜结构域的质粒进行疫苗接种以预防r-p185(+)可移植性癌细胞(TUBO)和乳腺癌发生的能力。在正常 BALB/c 小鼠中，DNA 疫苗接种可引发抗 r-p185 Ab，但仅产生边缘 CTL 反应性，并可防止 TUBO 细胞攻击。大量反应性浸润与 TUBO 细胞排斥有关，在转基因大鼠 Her-2/neu 基因 (BALB-neuT) 的 BALB/c 小鼠中，DNA 疫苗接种引起较低的抗 r-p185 Ab 反应，没有 CTL 活性，并且只能不完全地防止 TUBO 细胞，但显着阻碍了癌发生的进展。 33周龄时，当对照BALB-neuT小鼠在所有乳腺中显示可触及的肿瘤时，约60%的免疫小鼠是肿瘤Gee，并且肿瘤多重性显着降低。无肿瘤乳腺仍然表现出癌发生早期阶段的非典型增生，以及 r-p185 的显着下调，以及大量反应性浸润。然而，防止乳腺癌发生的 BALB-neuT 小鼠未能有效地抵抗 TUBO 细胞的攻击。这表明排斥可移植肿瘤所需的机制可能与抑制癌发生缓慢进展的机制不一致。
The ability of vaccination with plasmids coding for the extracellular and the transmembrane domain of the product of transforming rat Her-2/neu oncogene (r-p185) to protect against r-p185(+) transplantable carcinoma (TUBO) cells and mammary carcinogenesis was evaluated. In normal BALB/c mice, DNA vaccination elicits anti-r-p185 Ab, but only a marginal CTL reactivity, and protects against a TUBO cell challenge. Massive reactive infiltration is associated with TUBO cell rejection, In BALB/c mice transgenic for the rat Her-2/neu gene (BALB-neuT), DNA vaccination elicits a lower anti-r-p185 Ab response, no CTL activity and only incompletely protects against TUBO cells, but markedly hampers the progression of carcinogenesis. At 33 wk of age, when control BALB-neuT mice display palpable tumors in all mammary glands, about 60% of immunized mice are tumor Gee, and tumor multiplicity is markedly reduced. Tumor-free mammary glands still display the atypical hyperplasia of the early stages of carcinogenesis, and a marked down-modulation of r-p185, along with a massive reactive infiltrate. However, BALB-neuT mice protected against mammary carcinogenesis fail to efficiently reject a TUBO cell challenge. This suggests that the mechanisms required for the rejection of transplantable tumors may not coincide with those that inhibit the slow progression of carcinogenesis.