3D Printing Scaffold Vaccine For Antitumor Immunity

Cancer immunotherapy has revolutionized tumor therapy,recently,tumor vaccine has gradually attracted attention of researchers.By providing multiple tumor antigens,cancer vaccines can produce long-lasting anti-tumor immunity.At the same time,tumor vaccine combined with immune checkpoint blockade(ICB)therapy can significantly improve the therapeutic effects.However,cancer vaccines are still in their infancy.In clinical,the responses of most cancer vaccines are relatively weak.This may attribute to low uptake of immune cells,as well as low efficiency in antigen delivery and activation of immune responses.Here,we developed a 3D-printed scaffold vaccine which enhances immunotherapy by loading immunomodulators.The main research contents include the following:Chapter 1:Briefly introduced developments of 3D printed hydrogels in recent years and their applications in drug delivery.3D printing technology can combine with biomedicine,realizing treatments of various disease models.Meanwhile,summarized developments of tumor vaccines,discussed necessity and feasibility of this research;Chapter 2:Designed and manufactured of 3D printing ink,and further explored properties of material after loading with tumor antigen.Rapid manufacture and precise fabrication based on 3D printing technology realized fast and stable production of tumor vaccine;Explored the biosafety of 3D printed scaffold vaccines,monitored the main health indicators of mice after implantation of scaffolds,thus analyzed potential side effects and degradation performances of 3D printed scaffold vaccines in vivo;Chapter 3:3D printed scaffold vaccine can promote the maturation of DCs,as well as facilitating antigen presentation in vitro.In addition,scaffold vaccine further upregulated the secretion of cytokines in DCs;Chapter 4:After loading tumor immunomodulators,3D scaffold vaccines could recruit more immune cells in vivo.In addition,3D scaffold vaccine can activate immune cells more effectively,thus realize T cell-mediated immune responses;Compared with traditional hydrogels,3D scaffold vaccine with porous structure endowed similar functions compared with real lymphoid organs by recruitment of a great number of immune cells,leading to the formation of ’artificial tertiary lymphoid structures(aTLS)’,where is a promising site to enhance both humoral and cellular immune responses;Chapter 5:3D scaffold vaccine combined with ICB induced effective anticancer immunity.T cells infiltrated in tumor were up-regulated by synergistic effect,and induced T cells mediated anti-tumor immune responses;Through combining with clinical practices,we constructed personalized tumor vaccine after surgical resection.Confirmed personalized scaffold vaccine can prevent tumor recurrence and metastasis;Chapter 6:Summarized the shortcomings of this study,analyzed importance and necessity of this study,and discussed the future development direction in depth.In summary,in this study,we used 3D printing technology to construct 3D scaffold vaccine with special pore structure,which could recruit more immune cells in vivo and form "artificial tertiary lymphoid structure(aTLS)",thus enhancing humoral and cellular immune responses and achieving inhibition of tumor growth.3D scaffold vaccine combined with ICB could further improve anti-tumor efficacy.In addition,we further demonstrated personalized anti-tumor scaffold vaccines after surgery,proved that personalized scaffold vaccine can inhibit tumor growth and prevent cancer metastasis.In conclusion,3D-printed scaffold vaccines are expected to be a potential option for future cancer treatments.