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携带前列腺癌特异性抗原并以白细胞介素-12作为分子内佐剂的DNA疫苗的抗肿瘤作用

Antitumor Effect of a DNA Vaccine Harboring Prostate Cancer-Specific Antigen with IL-12 as an Intramolecular Adjuvant.

作者信息

Yang Yu, Shao Zhiqiang, Gao Jiangping

机构信息

Department of Urology, the First Affiliated Hospital of the General Hospital of the People's Liberation Army, Beijing, China.

出版信息

J Mol Microbiol Biotechnol. 2017;27(3):168-174. doi: 10.1159/000477245. Epub 2017 Aug 4.

Abstract

To improve the lower immune intensity of DNA vaccines, we developed a DNA vaccine based on prostate cancer-specific antigen (PSA), which has been suggested as a potential target for prostate cancer therapy, and enhanced the DNA vaccine potency using interleukin-12 (IL-12) as an intramolecular adjuvant. A series of DNA plasmids encoding human PSA, IL-12, and their conjugates was constructed and injected into female mice intramuscularly, followed by an electric pulse. The humoral and cellular immune responses after immunization were detected by ELISA and ELISPOT, respectively. To evaluate the therapeutic efficacy of these plasmids, a mouse model with a PSA-expressing tumor was constructed. Mice vaccinated with PSA-IL-12 plasmids elicited the strongest PSA-specific humoral and cellular immune responses. Furthermore, these vaccinations inhibited the growth of PSA-expressing tumors and prolonged mouse survival. These observations emphasize the potential of the IL-12 gene as an intramolecular adjuvant for DNA vaccines. Moreover, the vaccine based on PSA and IL-12 may be a promising treatment for prostate cancer.

摘要

为提高DNA疫苗较低的免疫强度,我们研发了一种基于前列腺癌特异性抗原(PSA)的DNA疫苗,PSA已被认为是前列腺癌治疗的潜在靶点,并使用白细胞介素-12(IL-12)作为分子内佐剂增强了DNA疫苗的效力。构建了一系列编码人PSA、IL-12及其缀合物的DNA质粒,并将其肌肉注射到雌性小鼠体内,随后进行电脉冲处理。免疫后分别通过ELISA和ELISPOT检测体液免疫和细胞免疫反应。为评估这些质粒的治疗效果,构建了表达PSA的肿瘤小鼠模型。接种PSA-IL-12质粒的小鼠引发了最强的PSA特异性体液免疫和细胞免疫反应。此外,这些疫苗接种抑制了表达PSA的肿瘤生长并延长了小鼠存活时间。这些观察结果强调了IL-12基因作为DNA疫苗分子内佐剂的潜力。此外,基于PSA和IL-12的疫苗可能是前列腺癌的一种有前景的治疗方法。

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