A conjugate of octamer-binding transcription factor 4 and toll-like receptor 7 agonist prevents the growth and metastasis of testis embryonic carcinoma.

Abstract

BACKGROUND:

The immune non-recognition is often the underlying cause of failure in tumor immunotherapeutic. This is because most tumor-related antigens are poorly immunogenic, and fail to arouse an efficient immune response against cancers. Here we synthesized a novel TLR7 agonist, and developed a safe and effective immunotherapeutic vaccine by conjugating this TLR7 agonist with the pluripotency antigen OCT4.

METHODS:

Purified recombinant OCT4 protein was covalently linked with a novel TLR7 agonist to form a TLR7-OCT4 conjugate (T7-OCT4). After conjugation, the in vitro release of IL-12 and IFN-γ was observed in spleen lymphocytes. Mice were immunized with TLR7-OCT4, and the release of IFN-γ, the percentages of CD3+/CD8+ T cells and the OCT4-specific cytotoxicity rates were measured. The immunized mice were challenged with mouse embryonic carcinoma (EC), and the tumor volume and tumor weight were determined. Blood routine examination was performed to evaluate the biosafety of TLR7 agonist and TLR7-OCT4 conjugate in mice.

RESULTS:

T7-OCT4 conjugate significantly increased the in vitro release of IL-12 and IFN-γ by mouse spleen lymphocytes. In addition, the release of IFN-γ, the percentages of CD3+/CD8+ T cells and the tumor-specific cytotoxicity rates in immunized mice were significantly higher. Importantly, in EC xenografted mice, immunization with T7-OCT4 conjugate decreased the growth of the tumor dramatically up to 90 %, as compared to mice immunized with OCT4 protein or TLR7 agonist alone. Furthermore, blood routine examination demonstrated that no abnormalities of the blood cells and components in the blood fluids were detected by T7-OCT4 and TLR7 agonist injections.

CONCLUSIONS:

Our results showed that conjugating OCT4 protein to the novel TLR7 agonist produced a vaccine which is effective and safe in preventing tumor growth in mice. Our results suggest that this type of vaccine formulation has great potentiality in preventive vaccines against OCT4 expressing tumors.

• Authors: Guimiao Lin, Xiaomei Wang, Wanxian Yi, Chuanxia Zhang, Gaixia Xu, Xiaomei Zhu, Zhiming Cai, Yu Liu, Yuwen Diao, Marie Chia-Mi Lin, Guangyi Jin
• Journal: Journal of translational medicine (J Transl Med) Vol. 13 Pg. 166 (May 20 2015) ISSN: 1479-5876 [Electronic] England
• PMID: 25990580 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Membrane Glycoproteins
• Octamer Transcription Factor-3
• Pou5f1 protein, mouse
• Recombinant Proteins
• Tlr7 protein, mouse
• Toll-Like Receptor 7
• Interleukin-12
• Interferon-gamma

Topics

• Animals
• Antigens, Neoplasm (immunology)
• CD8-Positive T-Lymphocytes (cytology)
• Carcinoma, Embryonal (metabolism, prevention & control)
• Interferon-gamma (metabolism)
• Interleukin-12 (metabolism)
• Lymphocytes (cytology)
• Male
• Membrane Glycoproteins (agonists, chemistry)
• Mice
• Mice, Inbred BALB C
• Neoplasm Metastasis
• Neoplasm Transplantation
• Octamer Transcription Factor-3 (chemistry)
• Recombinant Proteins (metabolism)
• Spleen (metabolism)
• T-Lymphocytes, Cytotoxic (cytology)
• Testicular Neoplasms (metabolism, prevention & control)
• Time Factors
• Toll-Like Receptor 7 (agonists, chemistry)