Construction and anti-tumor efficacy of a peptide vaccine that targets calcium-binding protein S100A9 / 药学学报

Calcium-binding protein S100A9 is closely related to inflammation and tumor invasion, and is one of the specific markers of myeloid-derived suppressor cells (MDSC). In this study, a recombinant polypeptide vaccine CTB-S100A9 targeting mouse calcium-binding protein S100A9 was constructed by fusion cholera toxin B subunit (CTB) with S100A9 gene. The CTB-S100A9 fusion protein was expressed in E coli. and purified by Ni+ affinity chromatography. Vaccinate the purified recombinant CTB-S100A9 protein supplemented with aluminum hydroxide adjuvant can break the autoimmune tolerance and produce high titer of S100A9 antibody in mice. Moreover, the S100A9 antibody produced by CTB-S100A9 vaccination is more specific and does not cross-react with S100A8. In the mouse 4T1 breast cancer model, CTB-S100A9 vaccination not only has significant tumor prevention effects, but also has significant tumor therapeutic effects. In addition, CTB-S100A9 significantly inhibited lung metastasis in 4T1 mice breast cancer model. Further analysis by flow cytometry showed that CTB-S100A9 vaccination can significantly reduce the tumor induced Treg cells and granulocyte-derived MDSC in 4T1 mice model, and reverse the tumor immunosuppressive environment, thereby promote the anti-tumor efficacy. The animal experiments in this study were carried out under the animal care guidelines approved by the Animal Ethics Committee of the Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine. This study shows that CTB-S100A9 is a good recombinant vaccine that targets the tumor immune-suppression environment and has great potential for the future clinical application.

Construction and anti-tumor efficacy of a pentameric peptide vaccine that targets S100A8 / 药学学报

Myeloid-derived suppressor cells (MDSC) play critical roles in immune escape of tumor. We hypothesized that elimination of tumor-induced MDSCs might help to block tumor growth. Therefore, we constructed a cholera toxin B based peptide vaccine that targets a MDSC surface marker S100A8. Immunized BALB/c mice with CTB-S100A8 plus aluminum hydroxide induced high titers of anti-S100A8 antibodies and reduced tumor burden significantly in 4T1 mice model. We also found the vaccination led to significant reduction of tumor-induced monocytic MDSC (M-MDSC), with no effect on innate MDSCs, dendritic cell (DC) and macrophage (Mφ), demonstrating that targeting tumor-induced MDSC may be a promising approach in cancer immunotherapy.