Pre-Clinical Studies of Dendritic Cell-Tumor Cell Fusion Vaccines to Treat Breast Cancer.

摘要

Dendritic cells (DC) are highly potent antigen-presenting cells that are gaining status as a preferred adjuvant for cancer vaccine immunotherapy. DC derive their potency from the expression of MHC class I and MHC class II molecules, costimulatory molecules and adhesion molecules that provide secondary signals for the stimulation of naive T cells, CD4+ T-helper cells, CD8+ cytotoxic T lymphocytes (CTLs), NK and NKT cells (1,2). Because DC have the capacity to take up various types of molecules, the cells can be loaded with tumor-associated antigens (TAAs) in various forms and applied as vaccines. A novel DC-based approach is vaccination with DC-tumor cell hybrids generated by fusion of tumor cells with DC to combine sustained tumor antigen expression with the antigen-presenting and immune stimulatory capacities of DC. In animal models, immunization with DC-tumor cell hybrids can effectively provide anti- tumor protection or eradicate established disease. Hybrids of autologous DC comprised of tumor cell lines or primary human tumor cells (including breast carcinoma cells) have been shown to induce CTL responses against autologous tumor cell types in vitro. Two recent phase I clinical trials for the treatment of renal cell carcinoma and glioma have demonstrated that vaccination with DC- tumor cell hybrids can safely induce anti-tumor immune responses in patients. Traditional fusion technology using polyethylene glycol (PEG) is hampered by a lack of reproducibility and difficulties in method standardization. As an alternative, electrofusion has been used for production of DC-tumor cell hybrids.