construction and evaluation of a combined cyclophosphamidenanoparticle anticancer vaccine建设和评估联合cyclophosphamidenanoparticle抗癌疫苗.pdfVIP

Journal of Cancer Therapy, 2011, 2, 384-393 doi:10.4236/jct.2011.23053 Published Online August 2011 (http://www.SciRP.org/journal/jct) Construction and Evaluation of a Combined Cyclophosphamide/Nanoparticle Anticancer Vaccine Kurt Andrew Yaeger, Robert Anthony Kurt Department of Biology, Lafayette College, Easton, USA. E-mail: kurtr@ Received June 9th, 2011; revised July 8th, 2011; accepted July 16th, 2011. ABSTRACT Tumor immunotherapy is a rapidly emerging form of cancer treatment. In the current study, a nanoparticle-based vac- cine 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-co- glycolic 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. Keywords : Nanoparticle Vaccine, Breast Cancer, Metastasis, 4T1 1. Introduction of overcoming such barriers have been established, pav- ing the way for more effective cancer vaccines. In theory, an adaptive immune response could efficiently DC