Abstract
Cervical cancer is the most common malignant tumor in females worldwide. Human papillomavirus (HPV) infection is associated with the occurrence of cervical cancer. Thus, developing an effective and low-cost vaccine against HPV infection, especially in developing countries is an important issue. In this study, a novel HPV L1-E7 fusion multiepitope construct designed by immunoinformatics tools was expressed in bacterial system. HEK-293T cells-derived exosomes were generated and characterized to use as a carrier for crocin and curcumin compounds. The exosomes loaded with crocin and curcumin compounds as a chemotherapeutic agent (ExoCrocin and ExoCurcumin) were used along with the L1-E7 polypeptide for evaluation of immunological and anti-tumor effects in C57BL/6 mouse model. In vitro studies showed that ExoCrocin and ExoCurcumin were not cytotoxic at a certain dose, and they could enter tumor cells. In vivo studies indicated that combination of the L1-E7 polypeptide with ExoCrocin or ExoCurcumin could produce a significant level of immunity directed toward Th1 response and CTL activity. These regimens showed the protective and therapeutic effects against tumor cells (the percentage of tumor-free mice: ~100%). In addition, both ExoCrocin and ExoCurcumin represented similar immunological and anti-tumor effects. Generally, the use of exosomal crocin or curcumin forms along with the L1-E7 polypeptide could significantly induce T-cell immune responses and eradicate tumor cells.
Highlights
Cervical cancer is the fourth most common cancer in women, ranking after breast cancer, colorectal cancer and lung cancer, respectively [1]
Some examples of peptideMHC interactions between mice MHC class I alleles and cytotoxic T lymphocytes (CTL) epitopes were shown in S1 Fig. Subsequently, total 30 models were generated for each molecular docking between the L1-E7 multiepitope construct and Toll-like receptors (TLRs)-2, TLR-3, TLR-4, TLR-5, TLR-8, and TLR-9 receptors using ClusPro 2.0
The interaction models with the lowest energy scores were selected as shown in S2 Fig. The lowest energy levels achieved for TLR-2/ TLR-3/ TLR-4/ TLR-5/ TLR-8/ TLR9-multiepitope construct interaction were -998, -1101.9, -1112.5, -1484, -1148.5, and -1114.6, respectively indicating the highest binding affinity among the docked complexes
Summary
Cervical cancer is the fourth most common cancer in women, ranking after breast cancer, colorectal cancer and lung cancer, respectively [1]. Cervical cancer is caused by persistent infection with a high-risk type of human papillomavirus (hrHPV; 84% of all HPV-related cancers worldwide; [2]). The World Health Organization (WHO) recommended HPV vaccines as a main strategy to suppress HPV-related diseases especially cervical cancer (WHO, 2016). The coverage of HPV types was limited in these vaccines, and their use in pregnant women was not advised. Development of vaccines with broader preventive and therapeutic effects and better safety profile is recommended [3]. The current standard of care for cervical cancer is chemo-radiation therapy (CRT), it has a major negative effect on the quality of life for patients and sometimes with a low survival rate. There is an urgent need to develop an effective and easy therapy against cervical cancer in the world [4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
