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.

scholarly journals Cancer–testis antigen expression in triple-negative breast cancer

2011 ◽  
Vol 22 (1) ◽  
pp. 98-103 ◽  
Author(s):  
G. Curigliano ◽  
G. Viale ◽  
M. Ghioni ◽  
A.A. Jungbluth ◽  
V. Bagnardi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Antigen Expression ◽  
Cancer Testis Antigen ◽  
Cancer Testis

S-nitrosylation of CYR61 protein reduces triple-negative breast cancer metastasis ability

2020 ◽  
Author(s):  
Lee Jia ◽  
Yusheng Lu ◽  
Sudan He ◽  
Huanzhang Xie ◽  
Chunlian Zhong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mass Spectrometry ◽  
Intravenous Injection ◽  
Triple Negative Breast Cancer ◽  
Cancer Metastasis ◽  
Triple Negative ◽  
3D Structure ◽  
Protein S ◽  
Adhesion Assay ◽  
Biotin Switch

Abstract BackgroundTriple-negative breast cancer (TNBC) is the most difficult cancer to be treated. TNBC expresses high level of matricellular cysteine-rich protein CYR61/CCN1 that plays a key role in producing cancer metastases and is an important target for metastasis chemoprevention. Nitric oxide (NO) can covalently bind to the thiol group of cysteines (termed S-nitrosylation) resulting in regulation of the targeted protein functions. MethodsProtein S-nitrosylation were detected by biotin-switch assay and western blotting assay. CYR61 protein S-nitrosylated sites and 3D structure were determined by mass spectrometry and MODELLER software. Adhesion assay, cell morphology assay, wound healing assay and transwell invasion assay were used to evaluate effects of CYR61 S-nitrosylation on the cell metastatic ability. In vivo metastasis activity of CYR61 S-nitrosylation were tested by intravenous injection and mammary xenograft implantation mouse metastatic models.ResultsS-nitrosylation by GSNO of CYR61 reached a plateau quickly and was confirmed by spectroscopic analysis and biotin-switch assay. Mass-spectrometry proteomic analysis revealed that S-nitrosylation predominantly occurred at Cys100, Cys117, Cys229 and Cys239, resulting in CYR61 structure relaxed and unstable evidenced by protein structure modeling. S-nitrosylation of MDA-MB-231 cells, their CYR61-overexpressed and CYR61–silenced counterparts significantly attenuated the metastatic ability of these cells, including their ability of adhesion, mobility, invasion, and interplay with platelets, and made the adhered cells unattached. The attenuation in metastatic ability proportionally increased with the degree of S-nitrosylation to CYR61 naturally-expressed or genetically-manipulated cells, and was demonstrated in mice, where, S-nitrosylation of these cell lines not only inhibited their acute seeding to lungs after an intravenous injection, but also inhibited the late development of these cells into the metastatic nodes after mammary xenograft implantation. Furthermore, orthotopically-implanted MDA-MB-231 developed mammary tumors and later lung metastasis; whereas, the same cells with S-nitrosylation developed no tumor and metastasis at all. Conclusionwe present the first evidence that S-nitrosylation of CYR61 can significantly inhibit metastatic aggressiveness of the TNBC MDA-MB-231 cells. This conceptual creative study opens a new avenue to prevent the most aggressive TNBC from metastases by S-nitrosylation to CYR61.

scholarly journals In Silico Analysis Guides Selection of BET Inhibitors for Triple-Negative Breast Cancer Treatment

2016 ◽  
Vol 15 (8) ◽  
pp. 1823-1833 ◽  
Author(s):  
Javier Pérez-Peña ◽  
Gemma Serrano-Heras ◽  
Juan Carlos Montero ◽  
Verónica Corrales-Sánchez ◽  
Atanasio Pandiella ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Triple Negative Breast Cancer ◽  
In Silico ◽  
Triple Negative ◽  
In Silico Analysis ◽  
Breast Cancer Treatment ◽  
Bet Inhibitors ◽  
Silico Analysis ◽  
Selection Of

High expression of MAGE-A10 cancer-testis antigen in triple-negative breast cancer

2011 ◽  
Vol 29 (3) ◽  
pp. 1586-1591 ◽  
Author(s):  
Badovinac Črnjević Tanja ◽  
Spagnoli Giulio ◽  
Juretić Antonio ◽  
Jakić-Razumović Jasminka ◽  
Podolski Paula ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
High Expression ◽  
Cancer Testis Antigen ◽  
Cancer Testis

scholarly journals An In Silico Analysis Identified FZD9 as a Potential Prognostic Biomarker in Triple-Negative Breast Cancer Patients

2021 ◽  
Vol 17 (1) ◽  
pp. 42-52
Author(s):  
Daniel Rodrigues de Bastos ◽  
Mércia Patrícia Ferreira Conceição ◽  
Ana Paula Picaro Michelli ◽  
Jean Michel Rocha Sampaio Leite ◽  
Rafael André da Silva ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
In Silico ◽  
Triple Negative ◽  
Prognostic Biomarker ◽  
Breast Cancer Patients

scholarly journals CTAG1A expression associates with survival in triple negative breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Molecular Subtype ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Free Survival ◽  
Significant Gene ◽  
Cancer Testis

We mined published microarray data (1) to understand the most significant gene expression differences in the tumors of triple negative breast cancer patients based on survival following treatment: dead or alive. We observed significant transcriptome-wide differential expression of cancer/testis antigen 1A, encoded by CTAG1A when comparing the primary tumors of triple negative breast cancer patients dead or alive. Importantly, CTAG1A expression was correlated with distant metastasis-free survival in basal subtype breast cancer, a molecular subtype sharing significant overlap with triple negative breast cancer. CTAG1A may be of relevance as a biomarker or as a molecule of interest in understanding the etiology or progression of triple negative breast cancer.

A phase 1b study of safety and immune response to PVX-410 vaccine alone and in combination with durvalumab (MEDI4736) in HLA-A2+ patients following adjuvant therapy for stage 2/3 triple negative breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS1126-TPS1126 ◽  
Author(s):  
Steven J. Isakoff ◽  
Sara M. Tolaney ◽  
Nadine M. Tung ◽  
Sylvia Adams ◽  
Hatem Hussein Soliman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Adjuvant Therapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Checkpoint Inhibitors ◽  
Peptide Vaccine ◽  
Rank Test ◽  
Paired Data ◽  
Phase 1B

TPS1126 Background: Stage 2-3 triple negative breast cancer (TNBC) remains at high risk for recurrence despite modern adjuvant therapy. An important role for the immune system in TNBC has recently emerged. Tumor infiltrating lymphocytes (TILs) are correlated with improved prognosis and several PD-1/PD-L1 checkpoint inhibitors, including Durvalumab (DUR), demonstrated activity in metastatic TNBC. Vaccines are a promising approach to further enhance the immune response in many cancers including TNBC. PVX-410 (PVX) is a novel tetra-peptide vaccine against XBP1 (2 splice variants), CD138 and CS1 that was safe and induced immune responses in a phase 1b study in smoldering myeloma. XBP1 and CD138 are also over-expressed in TNBC. Methods: This Phase 1b multi-center, single arm study will enroll 20 HLA-A2+ female patients (pts) following completion of all adjuvant therapy for stage 2-3 TNBC. Pts will receive 6 doses of 800ug PVX (emulsified in Montanide (SC) and co-administered with Hiltonol (IM)) at 2-week intervals, and 2 doses of DUR 1500mg IV at the 4th and 6th vaccine visits. Eligible pts must be between 1-6 months from completing adjuvant therapy, have no prior autoimmune disease, and have residual disease if neoadjuvant therapy was used. The primary objective is to determine the safety and tolerability of the combination, and the key secondary objective is to determine the immune response to PVX + DUR. If ≤1 pt in the first 6 has a protocol defined dose limiting toxicity within 4 weeks after the first DUR dose, accrual will continue to 20 pts. Immune response will be assessed at baseline, pre-dose 4 PVX/dose 1 DUR, and 4 weeks after completing protocol therapy. Paired data in 20 pts provides 90% power to see a shift of 0.75 standardized units from baseline to 4 weeks post treatment with the signed rank test. Immune response will be determined by a FACs based assay of antigen specific CD3+CD8+ T lymphocyte response and IFN-γ production (intracellular staining) in patient PBMCs. Additional correlative studies, including T-cell PD-1 and tissue PD-L1, XBP1, and CD138, are planned. Currently 4 pts are enrolled. Clinical trial information: NCT02826434.

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