Background: The tolerogenic homeostasis in Breast Cancer (BC) can be surpassed by rationally
designed immune-encouraging constructs against tumor-specific antigens through immunoinformatics
Objective: Availability of high throughput data providing the underlying concept of diseases and awarded
computational simulations, lead to screening the potential medications and strategies in less time and cost.
Despite the extensive effects of Placenta Specific 1 (PLAC1) in BC progression, immune tolerance,
invasion, cell cycle regulation, and being a tumor-specific antigen the fundamental mechanisms and
regulatory factors were not fully explored. It is also worth to design an immune response inducing construct
to surpass the hurdles of traditional anti-cancer treatments.
Methods and Result: The study was initiated by predicting and modelling the PLAC1 secondary and
tertiary structures and then engineering the fusion pattern of PLAC1 derived immunodominant predicted
CD8+ and B-cell epitopes to form a multi-epitope immunogenic construct. The construct was analyzed
considering the physiochemical characterization, safety, antigenicity, post-translational modification,
solubility, and intrinsically disordered regions. After modelling its tertiary structure, proteinprotein
docking simulation was carried out to ensure the attachment of construct with Toll-Like Receptor
4 (TLR4) as an immune receptor. To guarantee the highest expression of the designed construct in
E. coli k12 as an expressional host, the codon optimization and in-silico cloning were performed. The
PLAC1 related miRNAs in BC were excavated and validated through TCGA BC miRNA-sequencing
and databases; the common pathways then were introduced as other probable mechanisms of PLAC1
Conclusion: Regarding the obtained in-silico results, the designed anti-PLAC1 multi-epitope construct
can probably trigger humoral and cellular immune responses and inflammatory cascades, therefore
may have the potential of halting BC progression and invasion engaging predicted pathways.