Cancer and Stroma-Targeted Immunotherapny with a Genetically Modified DC Vaccine

摘要

While current DC vaccines are safe, their antitumor activity is limited. This is foremost due to the presence of regulatory T cells (Tregs), which create an immunosuppressive environment in breast cancer patients. In addition, there is increasing evidence that effective solid tumor vaccines have to target cancer cells as well as their supporting stroma. Thus, overcoming Treg mediated immune suppression and targeting the tumor stroma in addition to breast cancer cells may produce the desired increase in antitumor activity of DC vaccines for breast cancer. According to the task 1 in the approved statement of work, recombinant lentiviral vector expressing A20-shRNA, HER2 and FAP was prepared and 4T1.2-neu tumor bearing mice were immunized with the lentivirus transduced DC vaccine. We found the DC vaccine induced robust T cell responses against HER2 and FAP, resulting in enhanced antitumor effect. Thus, the DC vaccine that target not only HER2, but also Treg and FAP, might present the optimized DC vaccine strategy against HER2(plus) breast cancer.