Peptides of tetraspanin oncoprotein CD151 trigger active immunity against primary tumour and experimental lung metastasis

Autor: Wanzun Lin, Jun Liu, Juhui Chen, Jiancheng Li, Sufang Qiu, Jiayu Ma, Xiandong Lin, Lurong Zhang, Junxin Wu
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: EBioMedicine, Vol 49, Iss , Pp 133-144 (2019)
Druh dokumentu: article
ISSN: 2352-3964
DOI: 10.1016/j.ebiom.2019.10.025
Popis: Background: Active immunotherapy is an effective, long-lasting, cheap, and safe approach to suppress cancer progression; however, the key issue is to develop appropriate tumour vaccines. Oncoproteins are up-regulated under various stress conditions and promote cell survival. Oncoproteins and their immunogenic domains could serve well as tumour vaccines and prime the hosts’ active anti-tumour immunity. Methods: Proteomic and bioinformatic analyses were performed to identify potential tumour associated antigens (TAAs). Then, peptides derived from CD151 were designed and synthesized according to the major histocompatibility complex (MHC) I binding and immunogenicity. Cytotoxicity assay, flow cytometry, immunohistochemistry, and in vivo bioluminescence imaging were performed to assess the active anti-tumour immunity triggered by CD151 peptides in H22 primary hepatoma and experimental 4T1 breast cancer lung metastasis models. Findings: CD151 was identified as an ideal TAA based on proteomic and bioinformatic analyses. CD151 peptides as tumour vaccines triggered active anti-tumour immunity against H22 hepatoma and the lung metastasis of 4T1 breast cancer in two mouse models through the activation of CD8+IFNγ+ lymphocytes and the subsequent targeted cytotoxicity. Further, the peptides suppressed the negative regulators, myeloid-derived suppressor cells. Survival was prolonged for mice with lung metastases from CD151 peptide-immunised groups. Interpretation: The up-regulated oncoproteins in 8 Gy-irradiated tumour cells are good candidates for designing immunogenic peptides as tumour vaccines. Anti-tumour active immunity primed by peptides from CD151 may be an effective and safe approach to suppress cancer progression. Keywords: Tetraspanin CD151, Oncoprotein, Irradiation, Peptide vaccine, Active immunotherapy
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