Antitumor effect of oral cancer vaccine withBifidobacteriumdelivering WT1 protein to gut immune system is superior to WT1 peptide vaccine

72 Background: The gut microbiota plays an important role in shaping systemic immune responses. We have developed a WT1 oral cancer vaccine using a recombinant Bifidobacterium Longum ( B. Longum) as a platform for displaying murine WT1 protein ( B. Longum-mWT1). The Wilms’ tumor 1 (WT1) gene, which encodes a zinc finger transcription factor, is reportedly overexpressing in various tumors and one of the most promising tumor-associated antigens for cancer immunotherapy. In order to examine anti-tumor effects of this oral vaccine, we administered it orally into mice inoculated with WT1+-expressing brain tumor which doesn’t respond to existing treatment. Methods: The synthesized murine-WT1 gene (117-439 amino acid residues) was fused to galacto-N-biose/lacto-N-biose I binding protein (GLBP) coding gene. GLBP is a membrane protein on the wild-type B. Longum cell wall, which is used as an anchor to display antigen. The resulting plasmid carrying GLBP-WT1 was introduced into B. Longum by electroporation. We inoculated mouse glioma cell lines (Gl261) subcutaneously into the C57BL/6J. C57BL/6J mice received oral administration of B. Longum-mWT1 every day or subcutaneous administration of WT1126 peptide with montanide adjuvant on days 1, 8, 15, 22, 29, and 36. Results: The tumor volume of the mice treated with B. Longum-mWT1 (n = 5) was significantly smaller than that of the mice given WT1 peptide vaccine (n = 5) ( P < 0.05). The frequency of CD8+/WT1-tetramer+ CTLs was higher in B. Longum-mWT1 and WT1 peptide vaccine groups than in PBS group, and the high frequency was maintained in B. Longum-mWT1 group. In the mouse with B. Longum-mWT1, the frequency CD8+/WT1-tetramer+ CTLs in mesenteric lymph node and spleen was higher than that in Peyer’s patch. The number of invasive CD8+ T cells in brain tumor was higher in the B. Longum-mWT1 group than in the PBS group. B. Longum-mWT1 induced significantly higher in vitro cytotoxicity against Gl261 cells than WT1 peptide. Conclusions: We confirmed that B. Longum-mWT1 can induce strong cellular immunity and the maintenance of this effect. These results suggest that it is a novel oral anti-cancer agent for treating glioblastoma, for which no effective treatment has been developed.

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WT1 Protein-derived Peptide Vaccine DSP-7888

10.32388/b0yk3m ◽

2020 ◽

Author(s):

Keyword(s):

Peptide Vaccine ◽

Wt1 Protein

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Probiotics and the Gut Immune System: Indirect Regulation

Probiotics and Antimicrobial Proteins ◽

10.1007/s12602-017-9322-6 ◽

2017 ◽

Vol 10 (1) ◽

pp. 11-21 ◽

Cited By ~ 54

Author(s):

Giorgio La Fata ◽

Peter Weber ◽

M. Hasan Mohajeri

Keyword(s):

Immune System ◽

Gut Immune System

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Immunoinformatics Study on Early 4 Protein of Human Papillomavirus Type 16 for Cervical Cancer Vaccine Peptide Candidate

Jurnal Biodjati ◽

10.15575/biodjati.v4i2.5414 ◽

2019 ◽

Vol 4 (2) ◽

pp. 252-262

Author(s):

Yani Suryani ◽

Opik Taupiqurrohman ◽

Muhammad Yusuf ◽

Toto Subroto ◽

Sukma Nuswantara

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

Amino Acid ◽

Cancer Vaccine ◽

Vaccine Candidate ◽

Peptide Vaccine ◽

Human Papillomavirus Type 16 ◽

Cervical Cancer Vaccine ◽

Peptide Candidate

The aims of this study were to carry out testing of the early 4 protein of type 16 HPV through immunoinformatics meth-ods in an effort to get the peptide vaccine candidate for cervical cancer. The software used are IEDB-AR, CABSdock and Accelrys Discovery Study 4.5. Based on the analysis that sequence of ami-no acid lysine, leucine, leucine, glycine, serine, threonine, tryp-tophan, proline and threonine (KLLGSTWPT) and the sequence of amino acid tyrosine, tyrosine, valine, leucine, histidine, leucine, cysteine, leucine, alanine, alanine, threonine, lysine, tyrosine, pro-line and leucine (YYVLHLCLAATKYPL) are peptide vaccine can-didate for cervical cancer from the early 4 protein of HPV type 16

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Anlotininb as a Promising Inhibitor on Tumor Growth of Oral Squamous Cell Carcinoma Through Cell Apoptosis and Mitotic Catastrophe

10.21203/rs.3.rs-80678/v1 ◽

2020 ◽

Author(s):

Zhaoming Deng ◽

Wei Liao ◽

Wei Wei ◽

Guihua Zhong ◽

Chao He ◽

...

Keyword(s):

Gene Expression ◽

Cell Cycle ◽

Growth Factor ◽

Oral Cancer ◽

Cell Apoptosis ◽

Antitumor Effect ◽

Growth Factor Receptor ◽

Gene Expression Omnibus ◽

Mitotic Catastrophe

Abstract BackgroundOral squamous cell carcinoma (OSCC) has been one of the most malignant cancers in head and neck region. Anlotinib is a tyrosine kinase inhibitor targeting several receptors such as vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and c-Kit. Here we investigated whether Anlotinib have any antitumor effect on oral cancer and tried to explore and explain the possible mechanism.MethodsData from The Cancer Genome Atlas and the Gene Expression Omnibus and Gene Expression Omnibus database was collected to analyze the relationship between the expression of vascular epithelial growth factor receptor 2 and the overall survival rate of OSCC. Oral cancer cell lines Cal-27 and SCC-25 were cultured to conduct all the experiments. In vitro experiments such as CCK-8, colony formation, cell cycle assay and cell apoptosis assay were conducted to detect cell proliferation ability and the change of cell phase and apoptosis. Proteins concerning cell cycle and cell apoptosis were visualized via western blot. α-Tubulin were visualized via immunofluorescence to detect cells undergoing mitotic catastrophe. ResultsHigher expression of VEGFR-2 was significantly related to poorer prognosis. Experiment in vitro demonstrated that cell proliferation was significantly inhibited(p<0.05) after Anlotinib administration and G2/M arrest and apoptosis were both detected in both cell lines. Cycle-related proteins promoting cell cycle progression and proteins related to cell survival were downregulated in Anlotinib group compared to the control group. Cell-death-related biomarker and phosphorylated histone 3 were upregulated in expression in Anlotinib group. Abnormal spindle apparatus was observed in cells undergoing mitotic catastrophe. ConclusionAnlotinib could exert an antitumor effect on oral cancer cells lines via apoptotic pathway and mitotic catastrophe pattern, presenting a promising potential therapy for patients with OSCC.

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