Roles Of Dendritic Cell Vaccines For Hu-SCID B-cell Lymphoma Model And Breast Cancer Models

The SCID mouse is of particular interest because of the absence of mature and functional T and B lymphocytes. Thus, SCID mice can tolerate a graft with human cells and particularly those of purified peripheral blood mononuclear cells (PBMC) administered by intraperitoneal injection. The reconstituted SCID mice, which are also called humanized SCID (hu-SCID) mice, provide an optimal model for studying tumor immunotherapy in an in vivo animal system.Dendritic cells(DCs) play a critical role in the initiation of immune responses, and it makes them an attractive addition to cancer vaccine strategies. CD40, a member of TNFR superfamily, is a type I membrane glycoprotein, 5C11 is an agonist CD40 monoclonal antibody prepared in our department. When B lymphoma cell line Daudi is treated with 5C11 its biological behavior is changed, and proliferation inhibition occurred, cell cycle arrested, and the sensitivity to apoptosis enhanced. Experimental results indicated the significant therapeutic potential of 5C11. PD-L1 (B7-H1), a new member of the B7 family, could also inhibit T cell proliferation. Recently studies showed that blockage of PDL1-PD1 interaction could enhance anti-tumor response in vivo.In this study we focused on establishing hu-SCID mice B lymphoma model and breast cancer models to study the therapeutic effects of DC vaccines.1. Establishment and identification of hu-SCID mice modelHu-SCID was established after treated with CTX to inhibit the hemocytopoiesis. With successive 4-day intraperitoneal injection, human peripheral blood mononuclear cells (PBMC) were engrafted into SCID mice. After engraftment, in week 4, 8 and 12 a peripheral blood, spleen and liver tissues were harvested. Further analysis consists of the following 4 parts. 1) Human CD3~+, CD19~+ cells first detected in peripheral blood with inflorescence microscope; 2) The percentage of human CD3~+, CD19~+ cells in peripheral...