Prophylactic and therapeutic CSC-based vaccination reduced tumor growth, metastasis and enhanced survival in mouse model of breast cancer

Immunotherapy is a promising cancer treatment, but its effectiveness is limited by the lack of specific strategies to target cancer stem cells (CSCs). CSCs a rare tumor cell subpopulation, are thought to drive tumor recurrence, metastasis, and therapy resistance and developing targeting CSCs is needed. This study investigates the efficacy of a CSC-based vaccine in preventing and treating breast tumor growth and metastasis in a mouse model. 4T1-CSC was enriched by sphere formation and characterized by high expression of stemness genes using real-time PCR and higher in vivo tumorigenicity compared to parental cells. Whole CSC lysates were used as vaccine in prophylactic and therapeutic settings and their efficacy was compared with parental cells, normal saline and adjuvant-injected groups in terms of tumor growth, liver and lungs metastasis and survival. Additionally, the presence of antibodies against CSCs and parental cells was evaluated by flow cytometry and immunofluorescence staining in vaccinated mice. CSC enrichment was confirmed by higher stemness gene expression and tumorigenicity in spheroid cells. CSC-Prophylactic vaccination significantly reduced tumor growth, lung and liver metastasis and improved survival compared to parental cell and control groups. Therapeutic vaccination reduced tumor growth until day 15, increases in survival and decreases in metastasis. Both vaccinations showed that CSC-vaccinated mice sera reacted more intensely with parental cells than with spheroid cells. CSC-based immunizations significantly reduce tumor growth and metastasis, enhancing survival. These findings underscore the potential of CSC-targeted therapies in cancer treatment, necessitating further research to develop effective breast cancer treatments.