PT  - JOURNAL ARTICLE
AU  - Chen, Tingting
AU  - Liu, Kan
AU  - Xu, Jiangyao
AU  - Zhan, Tianying
AU  - Liu, Maixian
AU  - Li, Li
AU  - Yang, Zhiwen
AU  - Yuan, Shuping
AU  - Zou, Wenyi
AU  - Lin, Guimiao
AU  - Carson, Dennis A.
AU  - Wu, Christina C. N.
AU  - Wang, Xiaomei
TI  - Synthetic and immunological studies on the OCT4 immunodominant motif antigen-based anti-cancer vaccine
AID  - 10.20892/j.issn.2095-3941.2019.0224
DP  - 2020 Feb 15
TA  - Cancer Biology and Medicine
PG  - 132--141
VI  - 17
IP  - 1
4099  - http://www.cancerbiomed.org/content/17/1/132.short
4100  - http://www.cancerbiomed.org/content/17/1/132.full
SO  - Cancer Biol Med2020 Feb 15; 17
AB  - 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.