Immune-Mediated Eradication of Cancer Stem Cells via Polyspherex Microsphere-based Vaccination

摘要

The prognosis for patients with metastatic breast cancer remains poor. Standard radio-and chemotherapies are effective against the majority of cells within solid tumors, but have little impact on the cancer stem cells (CSC) that perpetuate tumor growth. Many studies have implicated CSC as being critically involved in metastatic tumor spread. Thus, finding a way to specifically eradicate CSC could lead to protection from metastatic tumor progression. In this study, we attempted to use the specificity of the immune system to eradicate CSC using a vaccination technique based upon loading highly purified CSC lysates onto nanoparticles made of poly-L-lactic-co-glycolic acid (PLGA particles), then injecting these particles into tumor-bearing mice. Due to the low numbers of isolatable CSC in growing tumors, this vaccination strategy failed. However, during our vaccination strategy optimization, we identified an approach based upon incorporation of bulk tumor lysates into PLGA nanoparticles that was highly effective at eliminating metastatic breast tumors from the lungs of mice. This approach is under further investigation.