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 (αCD40), 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. αCD40 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 αCD40 was significantly potentiated by their co-incorporation onto the MWNTs. Furthermore, MWNT remarkably improved the ability of co-loaded OVA, CpG and αCD40 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 αCD40 could be a competent approach for efficient tumours eradication.
['Hassan|Hatem A F M|HA|', 'Smyth|Lesley|L|', 'Wang|Julie T-W|JT|', 'Costa|Pedro M|PM|', 'Ratnasothy|Kulachelvy|K|', 'Diebold|Sandra S|SS|', 'Lombardi|Giovanna|G|', 'Al-Jamal|Khuloud T|KT|']
D000818:Animals D000938:Antigen-Presenting Cells D019496:Cancer Vaccines D045744:Cell Line, Tumor D007167:Immunotherapy D051379:Mice D053769:Nanocapsules D037742:Nanotubes, Carbon D009374:Neoplasms, Experimental D010047:Ovalbumin D016896:Treatment Outcome
Vaccine delivery Carbon nanotubes Cancer vaccines Dendritic cells Nanomedicine