An Efficient And Multi-functional Artificial Antigen-presenting Cells Based On Biomimetic Magnetosomes For T Cell Therapy

Adoptive T cell therapy?ACT?have been a promising platform for their high potential in cancer immunotherapy.As the core of ACT,the artificial antigen-presenting cell-based adoptive T cell therapy which mainly simulates natural DCs in vitro,has been focus on constitution of artificial antigen-presenting cells?aAPC?with high antigen presenting ability.The aAPC platform described here could be well applied in vitro activation and amplification of cytotoxic T Lymphocytes?CTLs?,which could perform superior anti-tumor activity subsequently.In recent years,biomedical applications of nanomaterials have paved the way for construction aAPC.Thus far,a variety of material have been constructed for aAPC,from fluidic lipid bilayer-containing systems to rigid separable particles,such as magnetic particles,carbon nanotube bundles and liposomes.Despite the extensive data supporting the efficacy of these materials,unavoidable bioavailability and low antigen presentation efficiency limited their application.Furthermore,in adoptive T cell therapy,apart from the immune activity of CTLs,the ability to target lesion appear vital in particular in view of its impact on therapeutic effect.Meanwhile,as a prerequisite for controlling the migration process of CTLs in vivo,real-time tracing of CTLs has been drawing growing attention.At present,there are few reports on CTLs targeting,and the in vivo tracing technology for CTLs is also urgent to be resolved.Numerous issues has limited the application of aAPC-based adoptive T cells.To overcame this obstacle,we developed a novel aAPC which could be well applied in tumor immunotherapy based on biomimetic magnetosomes.Briefly,we cloaked the superparamagnetic nanoparticles with leukocyte membrane,and then we cross-linked signal 1,peptide-MHC,and signal 2,anti-CD₂₈ onto the magnetosomes to constitution a aAPC.In vitro,this aAPCs platform performed well in activation and amplification of CTLs,which show superior anti-tumor efficiency subsequently either in cell or tumor tissue.Moreover,we found the aAPC-CTLs complex while the aAPC were not separated after CTLs expanding showed superior anti-tumor efficiency in adoptive T cell transfusion of mice.Furthermore,introduction of partial magnetic field could enhance the treatment effect.Meanwhile,it is possible to trace the intratumoral enrichment of CTLs by MRI.In this study,the aAPC plaform describe here innovatively ultilizing the excellent biocompatibility and outstanding membrane fluidity of leukocyte membrane,vividly simulated the natural APC in the topological structure,and behaved excellent antigen presentation performance.Besides,combining with the intrinsic potential of leukocyte membrane and the inherent magnetic properties of aAPC,we successfully introduced the transfusion model of"aAPC-CTLs"complex for adoptive T cell therapy,which showed superior tumor targeting ability under the double sector of inflammation tendency and magnetic field-induced.Besides,we maximizes the intrinsic properties of the aAPC-the MRI imaging potential,and achieves noninvasive tracing of transfused CTLs in animal models,creatively imparting targeted and therapeutic potential for adoptive T cell therapy.