TY - JOUR T1 - Synthetic and immunological studies on the OCT4 immunodominant motif antigen-based anti-cancer vaccine JF - Cancer Biology and Medicine JO - Cancer Biol Med SP - 132 LP - 141 DO - 10.20892/j.issn.2095-3941.2019.0224 VL - 17 IS - 1 AU - Tingting Chen AU - Kan Liu AU - Jiangyao Xu AU - Tianying Zhan AU - Maixian Liu AU - Li Li AU - Zhiwen Yang AU - Shuping Yuan AU - Wenyi Zou AU - Guimiao Lin AU - Dennis A. Carson AU - Christina C. N. Wu AU - Xiaomei Wang Y1 - 2020/02/15 UR - http://www.cancerbiomed.org/content/17/1/132.abstract N2 - 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. ER -