论文部分内容阅读
Objective:Cancer stem cell is one of the important causes of tumorigenesis as well as a drug target in the treatment of malignant tumor.However,at present,there is no immune vaccine targeting these cells.Octamer-binding transcription factor 4 (OCT4),a marker of embryonic stem cells and germ cells,often highly expresses in the early stages of tumorigenesis and is therefore a good candidate for cancer vaccine development.Methods:To identify the optimal carrier and adjuvant combination,we chemically synthesized and linked three different OCT4 epitope antigens to a carrier protein,keyhole limpet hemocyanin (KLH),combined with Toll-like receptor 9 agonist (TLR9).Results:Immunization with OCT4-3 + TLR9 produced the strongest immune response in mice.In prevention assays,significant tumor growth inhibition was achieved in BABL/c mice treated with OCT4-3 + TLR9 (P ＜ 0.01).Importantly,the results showed that cytotoxic T lymphocyte activity and the inhibition of tumor growth were enhanced in mice immunized with OCT4-3 combined with TLR9.Meanwhile,multiple cytokines [such as interferon (IFN)-γ (P ＜ 0.05),interleukin (IL)-12 (P ＜ 0.05),IL-2 (P ＜ 0.01),and IL-6 (P ＜ 0.05)] promoting cellular immune responses were shown to be greatly enhanced in mice immunized with OCT4-3 + TLR9.Moreover,we considered safety considerations in terms of the composition of the vaccines to help facilitate the development of effective next-generation vaccines.Conclusions:Collectively,these experiments demonstrated that combination therapy with TLR9 agonist induced a tumor-specific adaptive immune response,leading to the suppression of primary tumor growth in testis embryonic carcinoma.