Control of human mesothelin-expressing tumors by DNA vaccines
Control of human mesothelin-expressing tumors by DNA vaccines
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DOI：
10.1038/sj.gt.3302974
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发表时间：
2007-08-01
期刊：
影响因子：
5.1
通讯作者：
Hung, C-F
中科院分区：
文献类型：
--
作者：
Chang, C-L;Wu, T-C;Hung, C-F
间皮素已被认为是开发抗原特异性癌症免疫疗法的潜在理想靶抗原，用于控制表达间皮素的癌症，如卵巢癌、间皮瘤和胰腺癌。在本研究中，我们利用编码人间皮素的DNA疫苗（pcDNA 3-Hmeso）来治疗用表达间皮素酶、表达Hmeso的卵巢癌细胞系Defb 29 Vegf-luc/ Hmeso攻击的C57 BL/6小鼠。随后通过非侵入性生物发光成像系统观察肿瘤攻击小鼠的治疗效果。其抗肿瘤作用的机制是通过对淋巴细胞亚群的清除以及对pcDNA 3-Hmeso-小鼠血清的过继转移。我们发现，pcDNA 3 Hmeso DNA疫苗接种产生了显着的抗肿瘤效果，并提高了小鼠的生存与Defb 29 Vegfluc/ Hmeso攻击。此外，我们发现CD 4+和CD 8 + T细胞免疫应答以及体液免疫应答对于在接种小鼠中观察到的抗肿瘤作用是重要的。我们的数据表明，用靶向Hmeso的DNA疫苗接种可以通过T细胞介导的免疫以及抗体介导的免疫对表达间皮素的肿瘤产生有效的抗肿瘤作用。
Mesothelin has been implicated as a potential ideal target antigen for the development of antigen-specific cancer immunotherapy for the control of mesothelin-expressing cancers such as ovarian cancer, mesothelioma and pancreatic adenocarcinoma. In the current study, we utilized a DNA vaccine encoding human mesothelin (pcDNA3-Hmeso) to treat C57BL/6 mice challenged with luciferase-expressing, Hmeso-expressing ovarian cancer cell line, Defb29 Vegf-luc/ Hmeso. The therapeutic effect of the tumor-challenged mice was followed by noninvasive bioluminescence imaging systems. The mechanism of the antitumor effect was characterized by depletion of subsets of lymphocytes as well as adopted transfer of serum from pcDNA3-Hmeso-mice. We found that vaccination with pcDNA3Hmeso DNA vaccine generates a significant antitumor effect and promotes survival in mice challenged with Defb29 Vegfluc/ Hmeso. Furthermore, we found CD4+ and CD8+ T-cell immune responses as well as the humoral immune responses are important for the observed antitumor effects in vaccinated mice. Our data indicated that vaccination with DNA vaccine targeting Hmeso could generate potent antitumor effects against mesothelin-expressing tumors through both T cell-mediated immunity as well as antibody-mediated immunity.