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Enhancement Of Immunotherapy For Cancer Associated Viruses By Using Biodegradable Adjuvants And Dendritic Cells

Posted on:2018-08-26Degree:DoctorType:Dissertation
Country:ChinaCandidate:Full Text:PDF
GTID:1364330566488044Subject:Biology
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The potential of the human tumor-associated viruses which are hepatitis C virus(HCV)and humanpappiloma virus(HPV)are emerging and needed for vaccine development.HCV is known to cause hepatitis and hepatocellular carcinoma.E2 envelope glycoprotein of hepatitis C virus type(HCV-E2)has been reported to bind human host cells,and it is a major target for developing anti-HCV vaccines.However,the therapeutic vaccine for infected patients still needs further development.In this study,we constructed HCV1b-E2 recombinant protein,a truncated form of peptide,to encapsulate in an effective vaccine adjuvant and delivery system by using poly D,L lactic-co-glycolide(PLGA)microspheres.Our results demonstrated that HCV1b-E2 peptide encapsulated in PLGA microspheres(HCV1b-E2-PLGA)immunized mice could induce a significant humoral and cell mediated immune response.Thus,HCV1b-E2-PLGA is shown to have adjuvant property and efficacy in the mice model,which is a good strategy to develop HCV prophylactic and therapeutic vaccines.For HPV vaccine,HPV-16 is known to cause cervical cancer.In this study,HPV therapeutic vaccines have been developed by using E7 oncoproteins of this virus targeted cell mediated immunity.Dendritic cells(DCs)are the professional antigen presenting cell and used for HPV therapeutic vaccines as the carrier or platform to induce antigen-specific cytotoxic T-cell responses.In this study,DCs were pulsed with HCV-16E7 protein adsorbed onto PLGA microspheres(E7PLGA)for the adjuvant of vaccines.E7 PLGA could show its efficacy in human cervical cancer system and to be the strategies to develop HPV therapeutic vaccine.The protein adsorption onto PLGA microspheres is better strategy to develop in both prophylactic and therapeutic vaccines due to its ability to induce helper T-cell expansion and cytotoxic T-cell expression.
Keywords/Search Tags:Cervical cancer vaccine, HPV16-E7 peptide, Hepatitis C virus(HCV), Therapeutic vaccine, PLGA microspheres, HCV-E2 peptide, Hepatocellular carcinoma
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