DNA vaccine encoding human papillomavirus antigens flanked by a signal peptide and a KDEL sequence induces a potent therapeutic antitumor effect
| Autor: | Roberto Montes de Oca Luna, José Alberto Barrón Cantú, José Juan Pérez Trujillo, Gabriel Figueroa Parra, Jaime García Juárez, Odila Saucedo Cárdenas, Rodolfo Garza Morales, Gerardo Enrique Muñoz Maldonado, Aracely García García, Humberto Rodríguez Rocha, María de Jesús Loera Arias |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
HPV16
0301 basic medicine Cancer Research Antigen Targeting Antigen presentation Biology DNA vaccination calreticulin 03 medical and health sciences 0302 clinical medicine Immune system Antigen antigen targeting signal peptide E7 E6 Endoplasmic reticulum Articles Cell cycle endoplasmic reticulum 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research biology.protein KDEL sequence Calreticulin |
| Zdroj: | Oncology Letters |
| ISSN: | 1792-1082 1792-1074 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|