Dual stimulation of antigen presenting cells using carbon nanotube-based vaccine delivery system for cancer immunotherapy

Although anti cancer immuno based combinatorial therapeutic approaches have shown promising results, efficient tumour eradication demands further intensification of anti tumour immune response. With the emerging field of nanovaccinology, multi walled carbon nanotubes (MWNTs) have manifested prominent potentials as tumour antigen nanocarriers. Nevertheless, the utilization of MWNTs in co-delivering antigen along with different types of immunoadjuvants to antigen presenting cells (APCs) has not been investigated yet. We hypothesized that harnessing MWNT for concurrent delivery of cytosine phosphate guanine oligodeoxynucleotide (CpG) and anti-CD40 Ig (alpha CD40), as immunoadjuvants, along with the model antigen ovalbumin (OVA) could potentiate immune response induced against OVA expressing tumour cells. We initially investigated the effective method to co-deliver OVA and CpG using MWNT to the APC. Covalent conjugation of OVA and CpG prior to loading onto MWNTs markedly augmented the CpG mediated adjuvanticity, as demonstrated by the significantly increased OVA specific T cell responses in vitro and in C57BL/6 mice. alpha CD40 was then included as a second immunoadjuvant to further intensify the immune response. Immune response elicited in vitro and in vivo by OVA, CpG and alpha CD40 was significantly potentiated by their co-incorporation onto the MWNTs. Furthermore, MWNT remarkably improved the ability of co-loaded OVA, CpG and alpha CD40 in inhibiting the growth of OVA expressing B16F10 melanoma cells in subcutaneous or lung pseudo metastatic tumour models. Therefore, this study suggests that the utilization of MWNTs for the co-delivery of tumour-derived antigen, CpG and alpha CD40 could be a competent approach for efficient tumours eradication. (C) 2016 The Author(s). Published by Elsevier Ltd.