第三代树突状细胞疫苗.pptx

Third generation dendritic cell vaccines for tumor immunotherapy Bernhard Frankenberger, Dolores J. Schendel ; 树突状细胞（Dendritic cells, DC）是机体功能最强的专职抗原递呈细胞(Antigen presenting cells, APC)，它能高效地摄取、加工处理和递呈抗原，未成熟DC（iDC）具有较强的抗原吞噬能力和迁移能力，成熟DC（mDC）高表达MHC和共刺激分子，DC能有效激活初始型T细胞，处于启动、调控、并维持免疫应答的中心环节。; DC免疫治疗通过采用病人自体的单核细胞在体外培养诱导生成DC，然后负载相应的肿瘤抗原，制成负载肿瘤抗原的DC，再将这些DC细胞注入体内后刺激体内的肿瘤杀伤性淋巴细胞增殖，发挥长期肿瘤监视作用和肿瘤杀伤作用，达到消灭肿瘤的目的。;There are three interactive signals impinge on lymphocyte responses : adequate DC presentation of MHC-peptide complexes for induction of antigen-specific T cells with simultaneous expression of activation ligands for stimulation of innate natural killer cells; (ii) dominant positive costimulation via molecules such as CD40, CD80, and CD86 (iii) secretion of cytokines that polarize immune responses in a Th1/Tc1direction to create optimal antitumor responses;Three interactive signals impinge on lymphocyte responses.;Signal 1: reproducible and efficient expression of TAAs in mDCs after transfer of in vitro transcribed RNA;RNA delivery of individual TAAs imbues mDCs with excellent capacity to reactivate effector-memory CTLs; The provision of ivt-RNA encoding a single TAA by electroporation allowed highly reproducible transfer and subsequent pMHC presentation by mDCs, providing them with an excellent capacity to specifically reactivate effector-memory CTLs.;Failure of total tumor-derived ivt-RNA to reconstitute important CTL ligands after transfer to mDCs;Presentation of multiple antigens by mDCs using pools of ivt-RNA;Signal 2: optimal costimulatory profiles are displayed by young mDCs generated in 3 days in vitro;The Properties of young mDCs;7d mDCs matured with maturation cocktail that include TNF, IL-1, IL-6 and PGE2.;3d mDCs VS 7d mDCs; 3d mDCs showed inferior CTL stimulation after electroporation of ivt-RNA unless alterate electroporation parame