TY - JOUR
T1 - Multi-antigen spherical nucleic acid cancer vaccines
AU - Teplensky, Michelle H.
AU - Evangelopoulos, Michael
AU - Dittmar, Jasper W.
AU - Forsyth, Connor M.
AU - Sinegra, Andrew J.
AU - Wang, Shuya
AU - Mirkin, Chad A.
N1 - Funding Information:
This material is based upon work supported by the Polsky Urologic Cancer Institute of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University at Northwestern Memorial Hospital, Edward Bachrach and the National Cancer Institute of the National Institutes of Health awards R01CA208783, R01CA257926 and P50CA221747. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. M.H.T. acknowledges support from Northwestern University’s Cancer Nanotechnology Training Program Award T32CA186897. M.E. was partially supported by the Dr John N. Nicholson Fellowship and the Alexander S. Onassis Public Benefit Foundation. Peptide synthesis was performed, with special thanks to M. Karver, at the Peptide Synthesis Core Facility of the Simpson Querrey Institute at Northwestern University, which has current support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-2025633). This work made use of the IMSERC MS facility at Northwestern University, with special thanks to S. Shafaie; this MS facility has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-2025633), the State of Illinois and the International Institute for Nanotechnology (IIN). This work was supported by the Northwestern University NUSeq Core Facility.
Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2023
Y1 - 2023
N2 - Cancer vaccines must activate multiple immune cell types to be effective against aggressive tumours. Here we report the impact of the structural presentation of two antigenic peptides on immune responses at the transcriptomic, cellular and organismal levels. We used spherical nucleic acid (SNA) nanoparticles to investigate how the spatial distribution and placement of two antigen classes affect antigen processing, cytokine production and the induction of memory. Compared with single-antigen SNAs, a single dual-antigen SNA elicited a 30% increase in antigen-specific T cell activation and a two-fold increase in T cell proliferation. Antigen placement within dual-antigen SNAs altered the gene expression of T cells and tumour growth. Specifically, dual-antigen SNAs encapsulating antigens targeting helper T cells and with externally conjugated antigens targeting cytotoxic T cells elevated antitumour genetic pathways, stalling lymphoma tumours in mice. Additionally, when combined with the checkpoint inhibitor anti-programmed-cell-death protein-1 in a mouse model of melanoma, a specific antigen arrangement within dual-antigen SNAs suppressed tumour growth and increased the levels of circulating memory T cells. The structural design of multi-antigen vaccines substantially impacts their efficacy.
AB - Cancer vaccines must activate multiple immune cell types to be effective against aggressive tumours. Here we report the impact of the structural presentation of two antigenic peptides on immune responses at the transcriptomic, cellular and organismal levels. We used spherical nucleic acid (SNA) nanoparticles to investigate how the spatial distribution and placement of two antigen classes affect antigen processing, cytokine production and the induction of memory. Compared with single-antigen SNAs, a single dual-antigen SNA elicited a 30% increase in antigen-specific T cell activation and a two-fold increase in T cell proliferation. Antigen placement within dual-antigen SNAs altered the gene expression of T cells and tumour growth. Specifically, dual-antigen SNAs encapsulating antigens targeting helper T cells and with externally conjugated antigens targeting cytotoxic T cells elevated antitumour genetic pathways, stalling lymphoma tumours in mice. Additionally, when combined with the checkpoint inhibitor anti-programmed-cell-death protein-1 in a mouse model of melanoma, a specific antigen arrangement within dual-antigen SNAs suppressed tumour growth and increased the levels of circulating memory T cells. The structural design of multi-antigen vaccines substantially impacts their efficacy.
UR - http://www.scopus.com/inward/record.url?scp=85147020682&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85147020682&partnerID=8YFLogxK
U2 - 10.1038/s41551-022-01000-2
DO - 10.1038/s41551-022-01000-2
M3 - Article
C2 - 36717738
AN - SCOPUS:85147020682
SN - 2157-846X
JO - Nature Biomedical Engineering
JF - Nature Biomedical Engineering
ER -
