The Construction And Functional Verification Of The PD-1/CD137L Fusion Protein

Cancer is still a worldwide threat to human being.The immune therapy has widely attention due to its remarkable treatment effect.The activation of T cell is the center process of immune response,In addition to the first activation signal,it also need a co-stimulate signal.To avoid excessive activation of T cells,the activated T cell evolves a set of negative feedback molecules to fight autoimmune reaction,such as:Programmed death receptor 1(PD1),cytotoxic T lymphocyte associated antigen 4(CTLA4).These molecules are not only very important to maintain the body's immune balance,also play an important role in the tumor immune escape.Now both anti-PD-1 and anti-PD-L1 monoclonal antibodies have been used in clinical trials for cancer patients.But the treatment effective has certain limitation.We hypothesize that a molecule blocking PD-1/PD-L1 negative signaling while activating CD137L/CD137 positive signaling might enhance antitumor immunity.In this study,we will generate a fusion protein containing both extracellular region of PD-1 and CD137L and investigate its blocking capability and antitumor efficacy in vitro.The construction of the fusion protein retrovirus vector and A549 cell line is successful.The fusion protein can bind to its ligand and promote the immune activation of T cells,it also can improve the lethal effect of the T cells.