Abstract：
AIMS:Active immunization with human vascular endothelial growth factor (hVEGF) vaccines provides a therapeutic option instead of bevacizumab therapy. However, the immunity to self-molecule is difficult to elicit due to immune tolerance. A bioactive peptide of two tandem repeats of mHSP70407-426 (M2) has exhibited potent adjuvant ability in our previous study, and the aim of this study was to explore whether M2 could assist hVEGF to display enhanced therapeutic anti-tumor effects. MAIN METHODS:The anti-tumor effects of hVEGF-M2 vaccine were evaluated in both H22 hepatocellular carcinoma and Lewis lung tumor models. CD31 analysis of excised tumors was used to evaluate anti-angiogenesis effects. The titers of anti-VEGF antibody was detected by ELISA and verified by western blot analyses, and the effects of immune sera on HUVEC differentiation were investigated by tube formation assay. KEY FINDINGS:M2 could assist hVEGF to exhibit more favorable therapeutic anti-tumor growth and metastasis effects than hVEGF. Meanwhile, high titer of anti-VEGF antibody was detected in hVEGF-M2 immunized mice sera by ELISA and verified by western blot analysis. Sera from hVEGF-M2 immunized mice could more significantly inhibit HUVEC tube formation than hVEGF immune serum. The hVEGF-M2-immune sera could more effectively inhibit H22 tumor growth and extend the survival rates of H22 tumor bearing mice than hVEGF-immune sera. CD31 analysis of the excised tumors verified a significant reduction in vessel density after hVEGF-M2 vaccination. SIGNIFICANCE:M2 could assist hVEGF to display enhanced anti-tumor effects, which are important for the further application of M2 to enhance antigen-specific immune responses.
journal_name
Life Scijournal_title
Life sciencesauthors
Xu M,Zhang Y,Dong W,Jiang L,Zhang J,Yu P,Xie S,Zhou Ldoi
10.1016/j.lfs.2018.03.039subject
Has Abstractpub_date
2018-05-15 00:00:00pages
102-110eissn
0024-3205issn
1879-0631pii
S0024-3205(18)30145-0journal_volume
201pub_type
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