Construction and Evaluation of a Combined Cyclophosphamide/Nanoparticle Anticancer Vaccine

Abstract

Tumor immunotherapy is a rapidly emerging form of cancer treatment. In the current study, a nanoparticle-based vaccine was constructed and the efficacy was assessed through analysis of immune cell populations, tumor growth rates, and metastasis. The vaccine was fabricated through encapsulation of plasmid DNA encoding the tumor-associated antigen Mage-b, and the TLR9 agonist CpG oligodeoxynucleotides by a biodegradable polymer, poly(L,D-lactic-coglycolic acid) (PLGA). The size and shape of the nanoparticles suggested that they were an appropriate size for uptake by professional antigen presenting cells; dendritic cells. Furthermore, effects of the immunopotentiating drug cyclo-phosphamide was included to decrease systemic populations of regulatory T cells (Treg); immune system sentinels that down-regulate immune responses. The vaccine was assessed using the 4T1 murine mammary carcinoma model which is a model for stage IV breast cancer. The combined cyclophosphamide/nanoparticle vaccine was shown to significantly reduce 4T1 tumor growth rates and lung metastasis in female BALB/c mice.