scholarly journals Immunoprotective effect of an in silico designed multiepitope cancer vaccine with BORIS cancer-testis antigen target in a murine mammary carcinoma model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Elham Mahdevar ◽  
Amirhosein Kefayat ◽  
Ashkan Safavi ◽  
Amirhossein Behnia ◽  
Seyed Hossein Hejazi ◽  
...  
Keyword(s):  
Cancer Vaccine ◽  
Mammary Carcinoma ◽  
Peptide Vaccine ◽  
Serum Levels ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
Cancer Testis Antigen ◽  
Strong Immune Response ◽  
Weight Decrease ◽  
Cancer Testis

AbstractIn our previous study, immunoinformatic tools were used to design a novel multiepitope cancer vaccine based on the most immunodominant regions of BORIS cancer-testis antigen. The final vaccine construct was an immunogenic, non-allergenic, and stable protein consisted of multiple cytotoxic T lymphocytes epitopes, IFN-γ inducing epitopes, and B cell epitopes according to bioinformatic analyzes. Herein, the DNA sequence of the final vaccine construct was placed into the pcDNA3.1 vector as a DNA vaccine (pcDNA3.1-VAC). Also, the recombinant multiepitope peptide vaccine (MPV) was produced by a transfected BL21 E. coli strain using a recombinant pET-28a vector and then, purified and screened by Fast protein liquid chromatography technique (FPLC) and Western blot, respectively. The anti-tumor effects of prophylactic co-immunization with these DNA and protein cancer vaccines were evaluated in the metastatic non-immunogenic 4T1 mammary carcinoma in BALB/c mice. Co-immunization with the pcDNA3.1-VAC and MPV significantly (P < 0.001) increased the serum levels of the MPV-specific IgG total, IgG2a, and IgG1. The splenocytes of co-immunized mice exhibited a significantly higher efficacy to produce interleukin-4 and interferon-γ and proliferation in response to MPV in comparison with the control. The prophylactic co-immunization regime caused significant breast tumors’ growth inhibition, tumors’ weight decrease, inhibition of metastasis formation, and enlarging tumor-bearing mice survival time, without any considerable side effects. Taking together, this cancer vaccine can evoke strong immune response against breast tumor and inhibits its growth and metastasis.

scholarly journals Cancer-testis antigen, BORIS based vaccine delivered by dendritic cells is extremely effective against a very aggressive and highly metastatic mouse mammary carcinoma

2011 ◽  
Vol 270 (2) ◽  
pp. 188-197 ◽  
Author(s):  
Mikayel Mkrtichyan ◽  
Anahit Ghochikyan ◽  
Hayk Davtyan ◽  
Nina Movsesyan ◽  
Dmitry Loukinov ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Mammary Carcinoma ◽  
Cancer Testis Antigen ◽  
Mouse Mammary Carcinoma ◽  
Cancer Testis

scholarly journals Increased serum levels of interleukin-6 in erythema nodosum leprosum suggest its use as a biomarker

2021 ◽  
Vol 87 ◽  
pp. 190-198
Author(s):  
Fátima Regina Vilani-Moreno ◽  
Vânia Nieto Brito-de-Souza ◽  
Sônia Maria Usó Ruiz Silva ◽  
Adriana Sierra Assêncio Almeida Barbosa ◽  
Beatriz Gomes Carreira Sartori ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Interleukin 2 ◽  
Serum Levels ◽  
Interleukin 10 ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
Interleukin 17 ◽  
Erythema Nodosum Leprosum ◽  
Multibacillary Leprosy ◽  
Necrosis Factor

Background: Erythema nodosum leprosum (ENL) is a frequent complication of multibacillary leprosy that can result in significant morbidity, including peripheral nerve damage and physical disability. The identification of possible serum markers could be a valuable tool for the early detection of ENL. Aims: The purpose of this study was to evaluate selected serum mediators involved in the innate and adaptive immune responses to identify possible immunomarkers for ENL. Methods: The levels of interleukin-2, interleukin-4, interleukin-6, interleukin-10, interleukin-17, interferon-γ, tumor necrosis factor, nitric oxide and anti-phenolic glycolipid-I antibodies were measured in the sera of leprosy patients with ENL [at the beginning of reaction (M0) and 1 month later (M1)], and then compared with the levels of the same markers in patients with untreated multibacillary leprosy without ENL (controls with leprosy: CTRL) and healthy individuals (healthy controls: CTRH). Results: Significantly higher levels of serum interleukin-6 were observed in M0 than in CTRL. In addition, pairwise comparisons showed higher levels of interleukin-6 in M0 compared to M1. Levels of tumor necrosis factor were higher in M0 than in CTRL, with no significant difference between M0 and M1. There were no differences in the levels of interleukin-2, interleukin-4, interleukin-10, interleukin-17 or interferon-γ between groups. The CTRL group had higher levels of nitric oxide compared to M0 and M1. High levels of anti-phenolic glycolipid-I were observed in M0, M1 and CTRL than in CTRH. Limitations: Three patients were not assessed at M1, decreasing the number of evaluated patients from 14 to 11. Conclusion: High-serum levels of interleukin-6 were observed during ENL, primarily in patients with more severe reactions; levels decreased after specific therapy, suggesting a role for this cytokine in pathogenesis and its utility as an ENL biomarker. Further studies should explore whether interleukin-6 could also be used as a predictive marker for ENL or as a specific target for its treatment.

scholarly journals In vivo evaluation of the efficacy of Sophora moorcroftiana alkaloids in combination with Bacillus Calmette–Guérin (BCG) treatment for cystic echinococcosis in mice

2017 ◽  
Vol 92 (6) ◽  
pp. 681-686 ◽  
Author(s):  
G. Zhang ◽  
J. Wang ◽  
Y. Luo ◽  
M. Yuan ◽  
Q. Gao ◽  
...  
Keyword(s):  
Cystic Echinococcosis ◽  
Secondary Infection ◽  
Serum Levels ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
Intragastric Administration ◽  
Bacillus Calmette Guerin ◽  
In Vivo Evaluation ◽  
Sophora Moorcroftiana

AbstractHuman cystic echinococcosis is a widespread, chronic, endemic, helminthic zoonosis caused by larval tapeworms of the species Echinococcus granulosus. At present, there is no rational and effective therapy for patients with echinococcosis. The present study evaluated whether the combination of alkaloids from Sophora moorcroftiana seeds (SMSa2) and Bacillus Calmette–Guérin (BCG) was effective in the treatment of experimental echinococcosis. After 20 weeks of secondary infection with protoscoleces, mice were randomly allocated to five groups and treated for 6 weeks by daily intragastric administration of albendazole (ABZ, 100 mg/kg), SMSa2 (100 mg/kg), BCG (abdominal subcutaneous injection at 5 × 106 CFU), SMSa2 + BCG (100 mg/kg SMSa2 and 5 × 106 CFU BCG) or normal saline (untreated group), respectively. The results indicated a significant reduction in the weight of hydatid cysts in the SMSa2 + BCG group compared with the untreated, SMSa2 and BCG groups. The rate of inhibition of hydatid cyst growth in the SMSa2 + BCG group (76.1%) was obviously increased compared with that in the SMSa2 (25.7%) and BCG (26.6%) groups, respectively. Compared with the untreated control, the SMSa2 + BCG group showed a non-significant increase in serum interleukin-4 (IL-4). Furthermore, the serum levels of interferon-γ (IFN-γ) between the untreated and SMSa2 + BCG groups were not statistically different. Therefore, the combination of alkaloids from S. moorcroftiana seeds and BCG can reduce cyst burden and is an effective therapeutic regimen against echinococcosis.

Serum levels of the cancer-testis antigen POTEE and its clinical significance in non-small cell lung cancer.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e22213-e22213
Author(s):  
Qi Wang ◽  
Xuefei Li ◽  
Shengxiang Ren ◽  
Ningning Cheng ◽  
Weijing Cai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Clinical Significance ◽  
Cell Lung Cancer ◽  
Serum Levels ◽  
Small Cell ◽  
Cancer Testis Antigen ◽  
Small Cell Lung ◽  
Cancer Testis

scholarly journals Cancer-Testis Antigen Peptide Vaccine for Cancer Immunotherapy: Progress and Prospects

2019 ◽  
Vol 12 (5) ◽  
pp. 733-738 ◽  
Author(s):  
Xiao Wei ◽  
Fangjun Chen ◽  
Kai Xin ◽  
Qin Wang ◽  
Lixia Yu ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Peptide Vaccine ◽  
Cancer Testis Antigen ◽  
Antigen Peptide ◽  
Cancer Testis

scholarly journals Serum Levels of the Cancer-Testis Antigen POTEE and Its Clinical Significance in Non-Small-Cell Lung Cancer

PLoS ONE ◽  
2015 ◽  
Vol 10 (4) ◽  
pp. e0122792 ◽  
Author(s):  
Qi Wang ◽  
Xuefei Li ◽  
Shengxiang Ren ◽  
Ningning Cheng ◽  
Mingchuan Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Clinical Significance ◽  
Cell Lung Cancer ◽  
Serum Levels ◽  
Small Cell ◽  
Cancer Testis Antigen ◽  
Small Cell Lung ◽  
Cancer Testis

scholarly journals Clinical Trial Using Cancer/Testis Antigen- and/or VEGFR1/2-Derived Peptide-Vaccine Cocktails

2013 ◽  
Vol 24 ◽  
pp. ix48
Author(s):  
T. Mori ◽  
S. Kisara ◽  
K. Hisamichi ◽  
C. Ishioka
Keyword(s):  
Clinical Trial ◽  
Peptide Vaccine ◽  
Cancer Testis Antigen ◽  
Cancer Testis

scholarly journals In silico design of a triple-negative breast cancer vaccine by targeting cancer testis antigens

Bioimpacts ◽  
2018 ◽  
Vol 9 (1) ◽  
pp. 45-56 ◽  
Author(s):  
Sepideh Parvizpour ◽  
Jafar Razmara ◽  
Mohammad M. Pourseif ◽  
Yadollah Omidi
Keyword(s):  
Breast Cancer ◽  
Cancer Vaccine ◽  
Triple Negative Breast Cancer ◽  
In Silico ◽  
Triple Negative ◽  
Structure Refinement ◽  
3D Structure ◽  
Peptide Vaccine ◽  
Dynamics Simulation ◽  
Cancer Testis

Introduction: Triple-negative breast cancer (TNBC) is an important subtype of breast cancer, which occurs in the absence of estrogen, progesterone and HER-2 receptors. According to the recent studies, TNBC may be a cancer testis antigen (CTA)-positive tumor, indicating that the CTA-based cancer vaccine can be a treatment option for the patients bearing such tumors. Of these antigens (Ags), the MAGE-A family and NY-ESO-1 as the most immunogenic CTAs are the potentially relevant targets for the development of an immunotherapeutic way of the breast cancer treatment. Methods: In the present study, immunoinformatics approach was used to design a multi-epitope peptide vaccine to combat the TNBC. The vaccine peptide was constructed by the fusion of three crucial components, including the CD8+ cytotoxic T lymphocytes (CTLs) epitopes, helper epitopes and adjuvant. The epitopes were predicted from the MAGE-A and NY-ESO-1 Ags. In addition, the granulocyte-macrophage-colony-stimulating factor (GM-CSF) was used as an adjuvant to promote the CD4+ T cells towards the T-helper for more strong induction of CTL responses. The components were conjugated by proper linkers. Results: The vaccine peptide was examined for different physiochemical characteristics to confirm the safety and immunogenic behavior. Furthermore, the 3D-structure of the vaccine peptide was predicted based on the homology modeling approach using the MODELLER v9.17 program. The vaccine structure was also subjected to the molecular dynamics simulation study for structure refinement. The results verified the immunogenicity and safety profile of the constructed vaccine as well as its capability for stimulating both the cellular and humoral immune responses. Conclusion: Based on our in-silico analyses, the proposed vaccine may be considered for the immunotherapy of TNBC.

Role of the TSLP–DC–OX40L pathway in asthma pathogenesis and airway inflammation in mice

2018 ◽  
Vol 96 (3) ◽  
pp. 306-316 ◽  
Author(s):  
Shuang Feng ◽  
Li Zhang ◽  
Xu-Hua Bian ◽  
Ying Luo ◽  
Guang-Hui Qin ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Immunoglobulin E ◽  
Serum Levels ◽  
Lavage Fluid ◽  
Treg Cells ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
Total Serum ◽  
Ifn Γ ◽  
Intratracheal Injection

This study aimed to explore the effect of the TSLP–DC–OX40L pathway in asthma pathogenesis and airway inflammation in mice. For this, 65 male BALF/c mice were distributed among the control, asthma, immunoglobulin G (IgG) + asthma (IgG, 500 μg/500 μL, intratracheal injection of 50 μL each time), LY294002 (OX40L inhibitor) + asthma (intratracheal injection of 2 mg/kg LY294002), and anti-TSLP + asthma (intratracheal injection of 500 μg/500 μL TSLP antibody, 50 μL each time) groups. ELISA was applied to measure the serum levels of immunoglobulin E (IgE), ovalbumin (OVA)-sIgE, interleukin-4 (IL-4), IL-5, IL-13, and interferon-γ (IFN-γ); flow cytometry was employed to detect Treg cells and dendritic cell (DC) and lymphopoiesis. RT–qPCR and Western blot assays were used to measure the levels of TSLP, OX40L, T-bet, GATA-3, NF-κB, p38, and ERK. Treatment with LY294002 and anti-TSLP resulted in increases in the numbers of total cells, eosinophils, neutrophils, and lymphocytes in the bronchoalveolar lavage fluid; total serum levels of IgE, OVA-sIgE, IL-4, IL-5, and IL-13; levels of DC cells; lymphopoiesis; and levels of TSLP, OX40L, GATA-3, NF-κB, p38, and ERK, whereas there were decreases in the levels of IFN-γ and CD4+CD25+Treg cells; CD4+Foxp3+Treg cells; and T-bet. The TSLP–DC–OX40L pathway may contribute to asthma pathogenesis and airway inflammation by modulating the levels of CD4+CD25+Treg cells and inflammatory cytokines.

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