Abstract
Triple-negative breast cancer (TNBC) is an aggressive, metastatic/invasive sub-class of breast cancer (BCa). Cell surface protein-derived multi-epitope vaccine-mediated targeting of TNBC cells could be a better strategy against the disease. Literature-based identified potential cell surface markers for TNBC cells were subjected to expression pattern and survival analysis in BCa patient sample using TCGA database. The cytotoxic and helper T-lymphocytes antigenic epitopes in the test proteins were identified, selected and fused together with the appropriate linkers and an adjuvant, to construct the multi-epitope vaccine (MEV). The immune profile, physiochemical property (PP) and world population coverage of the MEV was studied. Immune simulation, cloning in a suitable vector, molecular docking (against Toll-like receptors, MHC (I/II) molecules), and molecular dynamics simulations of the MEV was performed. Cell surface markers were differentially expressed in TNBC samples and showed poor survival in TNBC patients. Satisfactory PP and WPC (up to 89 and 99%) was observed. MEV significant stable binding with the immune molecules and induced the immune cells in silico. The designed vaccine has capability to elicit immune response which could be utilized to target TNBC alone/combination with other therapy. The experimental studies are required to check the efficacy of the vaccine.
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Acknowledgements
SK acknowledges Indian Council of Medical Research, India and Department of Science and Technology, India for providing financial support in the form Ad-hoc Project [No. 5/13/15/2020/NCD-III] and DST-SERB Grant [EEQ/2016/000350], respectively. SK also acknowledges DST-India for providing Departmental grant to the Department of Biochemistry, Central University of Punjab, Bathinda, India in the form of DST-FIST grant. KSP acknowledge Department of Biotechnology, India for providing DBT-Senior Research Fellowship. MS acknowledges Indian Council of Medical Research, India for providing ICMR-Senior Research fellowship [File No. 5/3/8/80/ITR-F/2020-ITR]. AKS acknowledges CSIR, India for providing CSIR-Senior Research Fellowship. SS and PC acknowledge Central Computing Facility, Indian Institute of Information Technology-Allahabad, India.
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SK conceptualized, supervised, the study and wrote the original draft of the manuscript; KSP, MS, and AKS curated the data and analyzed them. PC and SS generated MD simulation data and AKS analyzed it. SG critically read the manuscript and provided his valuable suggestions.
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Kumar, S., Shuaib, M., Prajapati, K.S. et al. A candidate triple-negative breast cancer vaccine design by targeting clinically relevant cell surface markers: an integrated immuno and bio-informatics approach. 3 Biotech 12, 72 (2022). https://doi.org/10.1007/s13205-022-03140-3
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DOI: https://doi.org/10.1007/s13205-022-03140-3