Novel Therapeutic Vaccine for Metastatic Mammary Carcinoma: Focusing MHC/Peptide Complexes to Lipid Rafts

摘要

Genetic engineering of tumor cells to express MHC class ll and subsequent use of said cells for treatment of established and metastatic tumors has yielded promising results in animal models for treatment of breast cancer. It is widely believed that the vaccine efficacy is due to the ability of such tumor cells to present tumor-specific antigens to 004+ T helper cells which activate the immune system to eradicate tumors. Next generation cell-based vaccines will have enhanced antigen presentation capabilities to further stimulate the anti-tumor immune response. It has recently been proposed that MHC class II molecules physically localize to cell-surface microdomains termed lipid rafts to enhance antigen presentation. Further more a correlation has been observed where cell-based tumor vaccines that have high levels of MHC class II in such rafts have higher efficacy than those with diminished or abolished levels of MHC class II in rafts. We propose to further target MHC class II molecules to lipid rafts to enhance the antigen presentation capabilities of tumor cell- based vaccines and than to use these modified vaccine cells for the treatment of established metastatic disease in mouse models of breast cancer.