TY - JOUR
T1 - Immunogenic analysis of epitope-based vaccine candidate induced by photodynamic therapy in MDA-MB-231 triple-negative breast cancer cells
AU - Serrano-Quintero, Alina
AU - Sequeda-Juárez, Alfonso
AU - Pérez-Hernández, C. Angélica
AU - Sosa-Delgado, Sara M.
AU - Mendez-Tenorio, Alfonso
AU - Ramón-Gallegos, Eva
N1 - Publisher Copyright:
© 2022
PY - 2022/12
Y1 - 2022/12
N2 - Background: Photodynamic therapy (PDT) is used to treat tumors through selective cytotoxic effects. PDT induces damage-associated molecular patterns (DAMPs) expression, which can cause an immunogenic death cell (IDC). In this study we identified potential immunogenic epitopes generated by PDT on triple-negative breast cancer cell line (MDA-MB-231). Methods: MDA-MB-231 cells were exposed to PDT using ALA (160 µg/mL)/630 nm at 8 J/cm2. Membrane proteins were extracted and separated by 2D PAGE. Proteins overexpressed were identified by LC-MS/MS and analyzed in silico through a peptide-HLA docking in order to identify the epitopes with more immunogenicity and antigenicity properties, as well as lower allergenicity and toxicity activity. The selected peptides were evaluated in response to macrophage activation and cytokine release by flow cytometry. Results: Differential proteins were overexpressed in the cells treated with PDT. A group of 16 peptides were identified from them, established in a rigorous selection by measuring antigenicity, immunogenicity, allergenicity, and toxicity in silico. The final selection was based on molecular dynamics, where 2 peptides showed the highest stability regarding to the RMSD value. These peptides were obtained from the proteins calreticulin and HSP90. The cytokine analysis evidenced macrophage activation by the releasing of TNF. Conclusion: Two peptides were identified from calreticulin and HSP90; proteins induced by PDT in MDA-MB-231 cells. Both epitopes showed immunogenic potential as a peptide-based vaccine for triple-negative breast cancer.
AB - Background: Photodynamic therapy (PDT) is used to treat tumors through selective cytotoxic effects. PDT induces damage-associated molecular patterns (DAMPs) expression, which can cause an immunogenic death cell (IDC). In this study we identified potential immunogenic epitopes generated by PDT on triple-negative breast cancer cell line (MDA-MB-231). Methods: MDA-MB-231 cells were exposed to PDT using ALA (160 µg/mL)/630 nm at 8 J/cm2. Membrane proteins were extracted and separated by 2D PAGE. Proteins overexpressed were identified by LC-MS/MS and analyzed in silico through a peptide-HLA docking in order to identify the epitopes with more immunogenicity and antigenicity properties, as well as lower allergenicity and toxicity activity. The selected peptides were evaluated in response to macrophage activation and cytokine release by flow cytometry. Results: Differential proteins were overexpressed in the cells treated with PDT. A group of 16 peptides were identified from them, established in a rigorous selection by measuring antigenicity, immunogenicity, allergenicity, and toxicity in silico. The final selection was based on molecular dynamics, where 2 peptides showed the highest stability regarding to the RMSD value. These peptides were obtained from the proteins calreticulin and HSP90. The cytokine analysis evidenced macrophage activation by the releasing of TNF. Conclusion: Two peptides were identified from calreticulin and HSP90; proteins induced by PDT in MDA-MB-231 cells. Both epitopes showed immunogenic potential as a peptide-based vaccine for triple-negative breast cancer.
KW - Calreticulin
KW - HSP90
KW - Peptide-based vaccine
KW - Photodynamic therapy
KW - Triple negative breast cancer
UR - http://www.scopus.com/inward/record.url?scp=85140920840&partnerID=8YFLogxK
U2 - 10.1016/j.pdpdt.2022.103174
DO - 10.1016/j.pdpdt.2022.103174
M3 - Artículo
C2 - 36602069
AN - SCOPUS:85140920840
SN - 1572-1000
VL - 40
JO - Photodiagnosis and Photodynamic Therapy
JF - Photodiagnosis and Photodynamic Therapy
M1 - 103174
ER -