Synthetic and immunological studies on the OCT4 immunodominant motif antigen-based anti-cancer vaccine

Tingting Chen, Kan Liu, Jiangyao Xu, et al.

Abstract


Objective: Cancer stem cell is one of the important causes of tumorigenesis as well as a drug target in the treatment of malignanttumor. However, at present,there is no immune vaccine targeting these cells. Octamer-binding transcription factor 4 (OCT4), amarker of embryonic stem cells and germ cells, often highly expresses in the early stages of tumorigenesis and is therefore a goodcandidate for cancer vaccine development.

Methods: To identify the optimal carrier and adjuvant combination, we chemically synthesized and linked three different OCT4epitope 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, significanttumor growth inhibition was achieved in BABL/c mice treated with OCT4-3 + TLR9 (P < 0.01). Importantly, the results showed thatcytotoxic T lymphocyte activity and the inhibition of tumor growth were enhanced in mice immunized with OCT4-3 combinedwith 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 developmentof effective next-generation vaccines.

Conclusions: Collectively, these experiments demonstrated that combination therapy with TLR9 agonist induced a tumor-specificadaptive immune response, leading to the suppression of primary tumor growth in testis embryonic carcinoma.

Cite this article as: Chen T, Liu K, Xu J, Zhan T, Liu M, Li M et al. Syntheticand immunological studies on the OCT4 immunodominant motif antigenbasedanti-cancer vaccine. Cancer Biol Med. 2020; 17: 132-141. doi: 10.20892/j.issn.2095-3941.2019.0224


Keywords


Cancer prevention; cancer immunology; OCT4; TLR9 agonist

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