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Cancer Cell Membrane-Coated Adjuvant Nanoparticles With Mannose Modification For Effective Anticancer Vaccination

Posted on:2019-06-03Degree:MasterType:Thesis
Country:ChinaCandidate:R YangFull Text:PDF
GTID:2404330545973450Subject:Biology
Abstract/Summary:PDF Full Text Request
Tumor vaccines for cancer prevention and treatment have attracted tremendous interests in the area of cancer immunotherapy in recent years.The current cancer immunotherapies,such as cancer vaccines,immune checkpoint blockade immunotherapy,adoptive cell therapy,have shown encouraging clinical results to treat different types of tumors.Among various classes of cancer immunotherapy strategies,cancer vaccines are featured with relatively low cost and high specificity.Therefore,it is very meaningful for us to develop a bionic nano tumor vaccine based on existing cancer vaccines.The research results are as follows:1.We designed and synthesized a bionic nanotumor vaccine(NP-R@M-M)using a melanoma tumor model.It is based on the Food and Drug Administration(FDA)certified D,L-lactide-co-glycolide(PLGA)carrier.Outsourced melanoma cell membrane antigens act as tumor-specific antigens.As we all know,there are mannose receptors on antigen-presenting cells.Therefore,we modified mannose on bionic nanotumor vaccines to enhance their targeting to antigen-presenting cells.The PLGA nanoparticles contained Imiquimod(R837),an agonist of Toll-like receptor 7,which was able to amplify the anti-tumor immune response.2.Firstly,at the in vitro level,the bionic nano vaccine(NP-R@MM)was incubated with BMDC and RAW 246.7 cells,respectively.The results showed that the bionic nano vaccine(NP-R@MM)has highly effective targeting of BMDC and RAW 246.7 cells.More significantly,bionic nano vaccine(NP-R@M-M)can significantly stimulate the maturation of BMDCThis work presents a novel nano bionic vaccine(NP-R@M-M)in combination with anti-PD-1 checkpoint-blockade,so as to effectively inhibit tumors and significantly treats tumors.3.At the in vivo level,a synthetic and optimized bionic nano vaccine(NP-R@MM)was used as a prophylactic vaccine to detect the effect of suppressing tumor in mice.The study found that the bionic nano vaccine(NP-R@MM)showed a very high strong inhibitory effect.Based on this,combined with anti-PD-1 checkpoint blocking therapy,as a therapeutic vaccine to detect the efficacy of the prevention and treatment of mouse melanoma,the study found that it can effectively treat melanoma.This paper proposes a novel bionic nano vaccine(NP-R@M-M)and develops a novel tumor treatment strategy combined with a checkpoint blocker that can effectively inhibit tumor growth and have a good therapeutic effect on tumors.
Keywords/Search Tags:Cancer immunotherapy, cancer vaccine, Bionic vaccine, checkpoint blockade
PDF Full Text Request
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