Preparation and antitumor effects of nanovaccines with MAGE-3 peptides in transplanted gastric cancer in mice

Yang, Jun; Li, Zhihua; Zhang, Jiajia; Chen, Rufu; Cheng, Liang-Zheng; Zhou, Qiujie; Yang, Linqi

doi:10.5732/cjc.009.10541

Cited by 34 publications

(21 citation statements)

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“…Clinical studies of adoptive immunotherapies have shown that longer survival was achieved in gastric cancer patients treated with chemotherapy in combination with tumorassociated lymphocytes or cytokineinduced killer cells than with chemotherapy alone [16,17] . As for cancer vaccines, nanoparticles with the melanomaassociated antigen 3 peptide show the ability to stimulate immune responses in vivo and kill mouse forestomach carcinoma cells [18] . Vaccination with human vascular endothelial growth factor receptors 1 and 2 combined with chemotherapy is well tolerated and highly effective in advanced or recurrent gastric cancer [19] .…”

Section: Discussionmentioning

confidence: 99%

Conjugation of toll-like receptor-7 agonist to gastric cancer antigen MG7-Ag exerts antitumor effects

Wang

Gao

Diao

et al. 2015

WJG

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AIM:To investigate the effects of our tumor vaccines on reversing immune tolerance and generating therapeutic response. METHODS:Vaccines were synthesized by solid phase using an Fmoc strategy, where a small molecule toll-like receptor-7 agonist (T7) was conjugated to a monoclonal gastric cancer 7 antigen mono-epitope (T7-MG1) or tri-epitope (T7-MG3). Cytokines were measured in both mouse bone marrow dendritic cells and mouse spleen lymphocytes after exposed to the vaccines. BALB/c mice were intraperitoneally immunized with the vaccines every 2 wk for a total of three times, and Basic StudyConjugation of toll-like receptor-7 agonist to gastric cancer antigen MG7-Ag exerts antitumor effects then subcutaneously challenged with Ehrlich ascites carcinoma (EAC) cells. Three weeks later, the mice were killed, and the tumors were surgically removed and weighed. Serum samples were collected from the mice, and antibody titers were determined by ELISA using an alkaline phosphate-conjugated detection antibody for total IgG. Antibody-dependent cell-mediated cytotoxicity was detected by the lactate dehydrogenase method using natural killer cells as effectors and antibody-labeled EAC cells as targets. Cytotoxic T lymphocyte activities were also detected by the lactate dehydrogenase method using lymphocytes as effectors and EAC cells as targets. RESULTS:Vaccines were successfully synthesized and validated by analytical high performance liquid chromatography and electrospray mass spectrometry, including T7, T7-MG1, and T7-MG3. Rapid inductions of tumor necrosis factor-α and interleukin-12 in bone marrow dendritic cells and interferon γ and interleukin-12 in lymphocytes occurred in vitro after T7, T7-MG1, and T7-MG3 treatment. Immunization with T7-MG3 reduced the EAC tumor burden in BALB/c mice to 62.64% ± 5.55% compared with PBS control (P < 0.01). Six or nine weeks after the first immunization, the monoclonal gastric cancer 7 antigen antibody increased significantly in the T7-MG3 group compared with the PBS control (P < 0.01). As for antibody-dependent cell-mediated cytotoxicity, antisera obtained by immunization with T7-MG3 were able to markedly enhance cell lysis compared to PBS control (31.58% ± 2.94% vs 18.02% ± 2.26%; P < 0.01). As for cytotoxic T lymphocytes, T7-MG3 exhibited obviously greater cytotoxicity compared with PBS control (40.92% ± 4.38% vs 16.29% ± 1.90%; P < 0.01). Core tip: Immunization with toll-like receptor-7 agonist conjugated with a monoclonal gastric cancer 7 antigen tri-epitope was efficacious in reversing tolerance and generating a therapeutic response in Ehrlich ascites carcinoma tumor-bearing mice. This occurred by enhancing the specific humoral and cellular immunity, which were displayed as higher antibody titers, antibodydependent cell-mediated cytotoxicity, and cytotoxic T lymphocyte activity. CONCLUSION:Wang XD, Gao NN, Diao YW, Liu Y, Gao D, Li W, Wan YY, Zhong JJ, Jin GY. Conjugation of toll-like receptor-7 agonist to gastric cancer antigen MG7-Ag exerts antitumor effects. World

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Section: Discussionmentioning

confidence: 99%

Conjugation of toll-like receptor-7 agonist to gastric cancer antigen MG7-Ag exerts antitumor effects

Wang

Gao

Diao

et al. 2015

WJG

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“…Additionally, the findings resulted from vaccination using dendritic cells in combination with HER-2/neu peptide have shown considerable tumor regression in gastric cancers by using vaccine-loaded nanoparticles containing over expressing HER-2/neu and MAGE-3 peptide/chitosan-deoxycholic acid. This method of therapy has been employed to simulate an antitumor immune response and could effectively lead to regression of tumor growth in a mouse model of gastric cancer [15]. During another investigation, the peptides derived from human vascular endothelial growth factor (VEGF) receptor 1 and vascular endothelial growth factor receptor 2 were used in combination with chemotherapy (S-1 plus cisplatin) [16] and activated a VEGF-specific cytotoxic lymphocyte response in patients with advanced gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

Design and in Silico Construction of New Efficient Antibodies Against Gastric Tumor-associated Antigens Towards Introducing Combined Strategy for Vaccine Tumor Therapy

Ghavami

Sakineh

Mazinani

et al. 2014

vacres

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“…MAGE expression can be induced by Helicobacter pylori [13]. In a preclinical setting where a nano-vaccine loaded with a MAGE-3 peptide was used, enhancement of the immune response in a mouse model of gastric cancer was observed resulting in tumor regression [14]. Other vaccine peptide developments could target tumor related antigens like HER2/neu , carcinoembryonic antigens, and even viral antigens such as HPV (Human papilloma virus), to enhance the immune response.…”

Section: Pathways Of Immune Targetsmentioning

confidence: 99%

The Future Prospects of Immune Therapy in Gastric and Esophageal Adenocarcinoma

Shaib

Nammour

Gill

et al. 2016

JCM

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The prognosis of esophageal cancers is poor and novel approaches are urgently needed. Despite improvements in outcomes with transtuzumab and ramucirumab, these improvements added an average of only 2 to 3 months with a median overall survival reported to be around 1 year. Comprehensive genomic sequencing has defined some molecular alterations with potential targets, but the majority of patients still do not benefit from druggable targets. Breakthroughs in immune checkpoint blockade have provided new therapeutic options in many cancers. Programmed death ligand 1 (PDL1) overexpression, a possible biomarker predicting response to immune checkpoint inhibitors, approaches forty percent in esophageal and gastric cancers. Translational and molecular studies have shown that esophageal cancers are possible candidate malignancies for immune checkpoint inhibition. In this review, we plan to highlight the mechanisms, preclinical, and early clinical data that provide insight on the role of immune therapeutics in esophageal cancers.

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Preparation and antitumor effects of nanovaccines with MAGE-3 peptides in transplanted gastric cancer in mice

Cited by 34 publications

References 0 publications

Conjugation of toll-like receptor-7 agonist to gastric cancer antigen MG7-Ag exerts antitumor effects

Conjugation of toll-like receptor-7 agonist to gastric cancer antigen MG7-Ag exerts antitumor effects

Design and in Silico Construction of New Efficient Antibodies Against Gastric Tumor-associated Antigens Towards Introducing Combined Strategy for Vaccine Tumor Therapy

The Future Prospects of Immune Therapy in Gastric and Esophageal Adenocarcinoma

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