Enhanced anti-tumor immunity against breast cancer induced by whole tumor cell vaccines genetically modified expressing alpha-Gal epitopes

摘要

Whole tumor cell vaccines have shown much promise, but demonstrated poor efficiency in phase III trials. In this study, we modified MDA-MB-231 tumor cells (MDA-MB-231(Gal+)) to express alpha-1, 3-galactosyltransferase (alpha-1, 3-GT) protein, to potentially enhance antitumor effect of whole tumor cell vaccines. MDA-MB-231 tumor cell vaccines were transfected with a reconstructed lentiviral containing alpha-1, 3-GT genes. Tumor growth, tumorigenesis and survival of Hu-NOD-SCID mice were observed when tumor-bearing mice were injected with tumor cell vaccines. Proliferation and apoptosis in MDA-MB-231 tumor xenografts were observed by immunohistochemistry. The levels of cytokine secretion in the serum of mice were tested by ELISA. CD8(+)T cells infiltrating tumors were assessed by flow cytometry. MDA-MB-231(Gal+) cells expressed active alpha-1, 3-GT and produced a-Gal in vitro. MDA-MB-231(Gal+) cell vaccines suppressed tumor growth and tumorigenesis in immunized Hu-NOD-SCID mice. Additionally, decrease of TGF-beta, IL-10 and increase of INF-gamma, IL-12 were observed in tumor cell vaccinated mice. Furthermore, the cell vaccines enhanced infiltration of cytotoxic CD8(+) T cells in the tumor microenvironment of immunized mice. The MDA-MB-231(Gal+) cell vaccines modified alpha-1, 3-GT genes improved the antitumor effect.