Immunotherapies are a promising treatment option especially for the management of TNBC owing to its higher levels of tumour-associated antigens together with higher mutational load. Of note, the administration of preventive vaccines in the early stage of the cancer holds promise for effective disease management. Therefore, the present study aimed to develop a novel multi-epitope peptide-based vaccination against TNBC employing SOX9, which has recently been recognized as a key regulator of TNBC metastasis. The immunodominant regions from the SOX9 protein were computed and assessed based on their ability to elicit both T and B lymphocyte mediated responses. The resultant epitopes were fused using appropriate linkers (EAAAK, KK, AAY and GPGPG) and adjuvant (50S ribosomal protein L7/L12) to enhance the vaccine's immunogenicity. The physicochemical properties and population coverage were also anticipated for the constructed vaccine. Adding together, docking and dynamics simulation studies were performed on the modelled vaccine against TLR-4 to provide insight into the stability. Finally, the designed vaccine was cloned into the pET28 (+) vector and immunological simulation studies were carried out. These results demonstrate that our designed vaccine had the potency to trigger humoral and cellular immune responses. Based on these collective evidences, the final proposed vaccine could be an interesting therapeutics for the management of TNBC in the near future. Schematic representation of an efficient vaccine design framework by combining the range of immunoinformatics strategies.
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http://dx.doi.org/10.1007/s11030-022-10539-w | DOI Listing |
Int J Mol Sci
December 2024
Research Group of Cancer Biomarkers, Biomedical Research Institute of Lleida (IRBLleida), Av. Alcalde Rovira Roure, 80, 25198 Lleida, Spain.
Triple-negative breast cancer (TNBC) represents roughly one-sixth of all breast cancer patients, but accounts for 30-40% of breast cancer deaths. Due to the lack of typical biomarkers exploited clinically for breast cancer, it remains very difficult to treat. Moreover, its intrinsic high heterogeneity and proneness to become resistant to the drugs administered makes the treatment management very challenging for oncologists.
View Article and Find Full Text PDFCells
December 2024
Department of Nursing, College of Nursing and Health Sciences, Jazan University, Jazan 45142, Saudi Arabia.
Advanced triple-negative breast cancer (TNBC) has poorer outcomes due to its aggressive behavior and restricted therapeutic options. While therapies like checkpoint inhibitors and PARP inhibitors offer some benefits, chemotherapy remains ineffective beyond the first line of treatment. Antibody-drug conjugates (ADCs) like sacituzumab govitecan-hziy (SG) represent a significant advancement.
View Article and Find Full Text PDFDev Cell
December 2024
Institut Curie, CNRS UMR 144, PSL University, 75005 Paris, France. Electronic address:
The phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway is frequently hyperactivated in triple-negative breast cancers (TNBCs) associated with poor prognosis and is a therapeutic target in breast cancer management. Here, we describe the effects of repression of mTOR-containing complex 1 (mTORC1) through knockdown of several key mTORC1 components or with mTOR inhibitors used in cancer therapy. mTORC1 repression results in an ∼10-fold increase in extracellular matrix proteolytic degradation.
View Article and Find Full Text PDFFront Immunol
December 2024
Translational Research Unit, Montpellier Cancer Institute Val d'Aurelle, Montpellier, France.
Background: In triple-negative breast cancer (TNBC), the most immunogenic breast cancer type, tumor-infiltrating lymphocytes (TILs) are an independent prognostic factor. Tertiary lymphoid structures (TLS) are an important TILs source, but they are not integrated in the current prognostic criteria.
Methods: In this retrospective study, TLS were assessed in hematein-eosin-saffron-stained (HES) histological sections from 397 early, chemotherapy-naive TNBC samples after primary surgical resection.
Immunopharmacol Immunotoxicol
February 2025
Cancer Research Lab, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth (Deemed to be University), Pune, India.
Objective: Triple-Negative Breast Cancer (TNBC), the most challenging subtype of Breast Cancer (BC), currently lacks targeted therapy, presenting a significant therapeutic gap in its management. Tumor Associated Macrophages (TAMs) play a significant role in TNBC progression and could be targeted by repolarizing them from M2 to M1 phenotype. Matairesinol (MAT), a plant lignan, has been shown to exhibit anticancer, anti-inflammatory and immunomodulatory activities.
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