Design and antitumor effect of nitrated T helper cell epitope vaccine CD47-NitraTh

LUO Jianhua; XIA Xuefei; YAO Wenbing; TIAN Hong

doi:10.11665/j.issn.1000-5048.20190516

Journal of China Pharmaceutical University > 2019 > 50(5): 614-621. > DOI: 10.11665/j.issn.1000-5048.20190516

LUO Jianhua, XIA Xuefei, YAO Wenbing, TIAN Hong. Design and antitumor effect of nitrated T helper cell epitope vaccine CD47-NitraTh[J]. Journal of China Pharmaceutical University, 2019, 50(5): 614-621. DOI: 10.11665/j.issn.1000-5048.20190516

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Design and antitumor effect of nitrated T helper cell epitope vaccine CD47-NitraTh

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Abstract

Using the genetic code extension technology, the immunogenic amino acid, p-nitrophenylalanine, was introduced into the universal T cell epitope and then fused with the fragment of the extracellular region of the immune checkpoint molecular CD47(19-140)to construct a vaccine targeting CD47. The CD47-NitraTh vaccine elicited high titer antibody in BALB/c mice, significantly inhibited CT26 colon cancer cells growth, and increased the ratio of spleen CD4⁺ T cells and CD8⁺ T cells. Meanwhile, it promoted the polarization of naï ve T cells to Th1 cells. Notably, CD47-NitraTh not only increased the proportion of tumour-infiltrating lymphocytes but also reduced the proportion of Treg cells in tumour tissues, which means that CD47-NitraTh vaccine can remodel the tumour immunosuppressive microenvironment. The results of this study suggested that CD47-NitraTh can be used as an effective tumour vaccine candidate.
- immune checkpoint,
- CD47,
- universal T cell epitope,
- tumor vaccine

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