Novel Vectors for Dendritic Cell Transduction

摘要

The development of vaccine approaches for breast cancer has the potential to provide an adjuvant therapy with low toxicity for patients at risk for disease recurrence. Polynucleotide vaccines have several advantages compared to traditional vaccines including the ability to elicit antigen-specific T cells, inherent immunogenicity, ability to modify the encoded antigen, and an excellent safety profile. However, clinical efficacy has been disappointing and strategies to enhance the potency of polynucleotide vaccines are needed. Adenoviral vectors also show promise for cancer vaccine approaches, but do not efficiently deliver genes to antigen-presenting cells such as dendritic cells (DCs). The authors are investigating novel vaccine strategies for breast cancer. The target tumor antigen is carcinoembryonic antigen (CEA), which is highly expressed in most breast tumors. DCs show promise for cancer immunotherapy due to their critical role in mediating immune response. Development of an optimal DC transduction protocol for tumor antigen presentation would represent a significant advancement in DC-based vaccination strategies. The authors are investigating methods of DC transduction and antigen modification that will elicit the most potent anti-tumor immune response. These studies have employed a nontransgenic mouse model of adenocarcinoma as well as a more stringent transgenic model. Appendices present three abstracts and two manuscripts of studies funded through this grant. The manuscripts are as follows: A DNA Vaccine Encoding Genetic Fusions of Carcinoembryonic Antigen (CEA) and Granulocyte/ Macrophage Colony-Stimulating Factor (GM-CSF), by Jose Lima et al.; Polynucleotide Immunization for Cancer Therapy, by Theresa V. Strong; and CD4O is Expressed on Ovarian Cancer Cells and Can Be Utilized for Targeting Adenoviruses, by Tanja Hakkarainen et al. (1 table, 2 figures, 5 refs.).