期刊
ONCOLOGY LETTERS
卷 13, 期 3, 页码 1569-1574出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ol.2017.5635
关键词
antigen targeting; calreticulin; DNA vaccination; E6; E7; endoplasmic reticulum; HPV16; KDEL sequence; signal peptide
类别
资金
- Research in Science and Technology [CN1096-11]
- Universidad Autonoma de Nuevo Leon
- National Council for Science and Technology [CB-10-158509]
- CONACYT
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-gamma 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.
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