TY - JOUR
T1 - In vivo gold nanoparticle delivery of peptide vaccine induces anti-tumor immune response in prophylactic and therapeutic tumor models
AU - Almeida, Joao Paulo Mattos
AU - Lin, Adam Yuh
AU - Figueroa, Elizabeth Raquel
AU - Foster, Aaron Edward
AU - Drezek, Rebekah Anna
N1 - Funding Information:
A. E. Foster and R. A. Drezek contributed equally to this work. This project was supported by the National Institutes of Health R01CA172836. J Almeida is also funded by the Keck Center of the Gulf Coast Consortia, on the Nanobiology Interdisciplinary Graduate Training Program, National Institute of Biomedical Imaging and Bioengineering (NIBIB) T32EB009379, as well as the National Science Foundation Graduate Research Fellowship #0940902 and the Howard Hughes Medical Institute Med into Grad fellowship.
Publisher Copyright:
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2015/3/25
Y1 - 2015/3/25
N2 - Gold nanoparticles (AuNPs) are promising vehicles for cancer immunotherapy, with demonstrated efficacy in immune delivery and innate cell stimulation. Nevertheless, their potential has yet to be assessed in the in vivo application of peptide cancer vaccines. In this study, it is hypothesized that the immune distribution and adjuvant qualities of AuNPs could be leveraged to facilitate delivery of the ovalbumin (OVA) peptide antigen and the CpG adjuvant and enhance their therapeutic effect in a B16-OVA tumor model. AuNP delivery of OVA (AuNP-OVA) and of CpG (AuNP-CpG) enhanced the efficacy of both agents and induced strong antigen-specific responses. In addition, it is found that AuNP-OVA delivery alone, without CpG, is sufficient to promote significant antigen-specific responses, leading to subsequent anti-tumor activity and prolonged survival in both prophylactic and therapeutic in vivo tumor models. This enhanced therapeutic efficacy is likely due to the adjuvant effect of peptide coated AuNPs, as they induce inflammatory cytokine release when cultured with bone marrow dendritic cells. Overall, AuNP-mediated OVA peptide delivery can produce significant therapeutic benefits without the need of adjuvant, indicating that AuNPs are effective peptide vaccine carriers with the potential to permit the use of lower and safer adjuvant doses during vaccination.
AB - Gold nanoparticles (AuNPs) are promising vehicles for cancer immunotherapy, with demonstrated efficacy in immune delivery and innate cell stimulation. Nevertheless, their potential has yet to be assessed in the in vivo application of peptide cancer vaccines. In this study, it is hypothesized that the immune distribution and adjuvant qualities of AuNPs could be leveraged to facilitate delivery of the ovalbumin (OVA) peptide antigen and the CpG adjuvant and enhance their therapeutic effect in a B16-OVA tumor model. AuNP delivery of OVA (AuNP-OVA) and of CpG (AuNP-CpG) enhanced the efficacy of both agents and induced strong antigen-specific responses. In addition, it is found that AuNP-OVA delivery alone, without CpG, is sufficient to promote significant antigen-specific responses, leading to subsequent anti-tumor activity and prolonged survival in both prophylactic and therapeutic in vivo tumor models. This enhanced therapeutic efficacy is likely due to the adjuvant effect of peptide coated AuNPs, as they induce inflammatory cytokine release when cultured with bone marrow dendritic cells. Overall, AuNP-mediated OVA peptide delivery can produce significant therapeutic benefits without the need of adjuvant, indicating that AuNPs are effective peptide vaccine carriers with the potential to permit the use of lower and safer adjuvant doses during vaccination.
KW - biodistribution
KW - cancer
KW - gold nanoparticles
KW - immune system
KW - immunotherapy
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U2 - 10.1002/smll.201402179
DO - 10.1002/smll.201402179
M3 - Article
C2 - 25354691
AN - SCOPUS:84925064063
SN - 1613-6810
VL - 11
SP - 1453
EP - 1459
JO - Small
JF - Small
IS - 12
ER -