Dendritic Cell Vaccine Therapy for Breast Cancer Micro-Metastases.

This project is studying the development of dendritic cell vaccines for immune therapy of breast cancer. We have developed techniques for isolation and immunogen loading of murine splenic dendritic cells which induced humoral and cellular immunity in a model system BSA. Translation to a tumor antigen CEA produced weak immune responses and antitumor effects. This system requires large amounts of immunogen to be effective. An alternate approach of developing gene transfer techniques to induce immunogen expression in dendritic cells is ongoing. We have developed a vector system using replication defective adenoviruses which is able to transfect dendritic cells as demonstrated with luciferase reporter gene. We have constructed a CEA vector Ad-CEA which induces CEA expression in cells in vitro it induced antibody to CEA following IV and IP injection but not antitumor effects TH-2 response. Generation of Ad-CEA dendritic cell vaccines are ongoing and already show evidence of CEA immune responses. We will examine these Ad-CEA dendritic cell vaccines as therapy in metastatic breast cancer models and examine strategies to switch the Ad-CEA alone system to a more effective immune response TH-1 response. We are constructing adenovirus-Erb-2 constructs as a second breast cancer relevant system.