DNA vaccine encoding human papillomavirus antigens flanked by a signal peptide and a KDEL sequence induces a potent therapeutic antitumor effect.
DNA vaccine encoding human papillomavirus antigens flanked by a signal peptide and a KDEL sequence induces a potent therapeutic antitumor effect.
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DOI：
10.3892/ol.2017.5635
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发表时间：
2017-03
期刊：
影响因子：
2.9
通讯作者：
Loera-Arias MJ
中科院分区：
文献类型：
--
作者：
Perez-Trujillo JJ;Garza-Morales R;Barron-Cantu JA;Figueroa-Parra G;Garcia-Garcia A;Rodriguez-Rocha H;Garcia-Juarez J;Muñoz-Maldonado GE;Saucedo-Cardenas O;Montes-De-Oca-Luna R;Loera-Arias MJ
细胞免疫反应通过识别并随后去除感染或恶性细胞，在根除细胞内感染和恶性细胞方面发挥着关键作用。有效的抗原呈递对于刺激免疫系统对抗恶性细胞至关重要。钙网蛋白（CRT）已被用于改善抗原呈递。然而，CRT过表达以前与胰腺癌和乳腺癌的发展有关。CRT在内质网（ER）中的输入和保留信号可用于克服CRT过表达。本研究描述了一种编码人乳头瘤病毒16型E6和E7抗原的DNA疫苗（SP-E6 E7 m-KDEL）的有效抗肿瘤作用。将该疫苗的效果与E6和E7抗原与人全长CRT（hCRT-E6 E7 m）融合的效果进行了比较。在本研究中，证明了SP-E6 E7 m-KDEL诱导干扰素-γ抗原特异性应答的有效性及其对肿瘤的治疗效果，其与针对与CRT融合的那些抗原的免疫一样有效。这种简化的策略，使用ER输入和保留信号肽将抗原引导至该细胞器，提供了传统疫苗的有效替代方案，更重要的是，提供了诱导治疗性抗肿瘤反应的安全有效的系统。
Cellular immune responses play a critical role in the eradication of intracellular infections and malignant cells through the recognition and subsequent removal of the infection or malignant cells. Effective antigen presentation is crucial for stimulating the immune system against malignant cells. Calreticulin (CRT) has been used to improve antigen presentation. However, CRT overexpression has been previously associated with the development of pancreatic and breast cancer. The import and retention signals of CRT in the endoplasmic reticulum (ER) can be used to overcome CRT overexpression. The present study describes the potent antitumor effect of a DNA vaccine encoding human papillomavirus type 16 E6 and E7 antigens flanked by ER import and retention signals (SP-E6E7m-KDEL). The effect of this vaccine was compared with that of E6 and E7 antigens fused to human full-length CRT (hCRT-E6E7m). In the present study, the effectiveness of SP-E6E7m-KDEL for inducing an interferon-γ antigen-specific, response and its therapeutic effect against tumors was demonstrated, which was as effective as immunization against those antigens fused to CRT. This simplified strategy, using ER import and retention signal peptides to direct antigens to this organelle, provides an efficient alternative to traditional vaccines and, more importantly, a safe and potent system to induce a therapeutic antitumor response.