title: Dual stimulation of antigen presenting cells using carbon nanotube-based vaccine delivery system for cancer immunotherapy.
abstract: 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.
authors.affiliation: Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, Franklin-Wilkins Building, London SE1 9NH, United Kingdom.
authors.forename: Hatem A F M
authors.initials: HA
authors.lastname: Hassan
authors.affiliation: Immunoregulation Laboratory, MRC Centre for Transplantation, King's College London, Guy's Hospital, London SE1 9RT, United Kingdom.
authors.forename: Lesley
authors.initials: L
authors.lastname: Smyth
authors.affiliation: Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, Franklin-Wilkins Building, London SE1 9NH, United Kingdom.
authors.forename: Julie T-W
authors.initials: JT
authors.lastname: Wang
authors.affiliation: Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, Franklin-Wilkins Building, London SE1 9NH, United Kingdom.
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Costa
authors.affiliation: Immunoregulation Laboratory, MRC Centre for Transplantation, King's College London, Guy's Hospital, London SE1 9RT, United Kingdom.
authors.forename: Kulachelvy
authors.initials: K
authors.lastname: Ratnasothy
authors.affiliation: Division of Immunology, Infection, and Inflammatory Diseases, King's College London, Guy's Hospital, London SE1 9RT, United Kingdom.
authors.forename: Sandra S
authors.initials: SS
authors.lastname: Diebold
authors.affiliation: Immunoregulation Laboratory, MRC Centre for Transplantation, King's College London, Guy's Hospital, London SE1 9RT, United Kingdom. Electronic address: giovanna.lombardi@kcl.ac.uk.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lombardi
authors.affiliation: Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, Franklin-Wilkins Building, London SE1 9NH, United Kingdom. Electronic address: khuloud.al-jamal@kcl.ac.uk.
authors.forename: Khuloud T
authors.initials: KT
authors.lastname: Al-Jamal
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D007167:Immunotherapy / Q000379:methods; D051379:Mice; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry*; D037742:Nanotubes, Carbon / Q000737:chemistry*; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D010047:Ovalbumin / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines; D053769:Nanocapsules; D037742:Nanotubes, Carbon; D010047:Ovalbumin
keywords: Cancer vaccines; Carbon nanotubes; Dendritic cells; Nanomedicine; Vaccine delivery