TY - JOUR
T1 - Efficient lymph node-targeted delivery of personalized cancer vaccines with reactive oxygen species-inducing reduced graphene oxide nanosheets
AU - Moon, James J.
AU - Xu, Cheng
AU - Hong, Hao
AU - Lee, Yonghyun
AU - Park, Kyung Soo
AU - Sun, Mingjiao
AU - Wang, Tianrui
AU - Aikins, Marisa E.
AU - Xu, Yao
N1 - Funding Information:
This work was supported in part by the NIH (R01AI127070, R01EB022563, R01CA210273, R01DK125087, U01CA210152). J.J.M. is supported by DoD/CDMRP Peer Reviewed Cancer Research Program (W81XWH-16-1-0369) and NSF CAREER Award (1553831). K.S.P. acknowledges financial support from the UM TEAM Training Program (DE007057 from NIDCR). We acknowledge the NIH Tetramer Core Facility (contract HHSN272201300006C) for the provision of MHC-I tetramers. Opinions interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense. Some figures were created by the authors with BioRender.com .
Publisher Copyright:
© 2020 American Chemical Society.
PY - 2020/10/27
Y1 - 2020/10/27
N2 - Therapeutic cancer vaccines require robust cellular immunity for the efficient killing of tumor cells, and recent advances in neoantigen discovery may provide safe and promising targets for cancer vaccines. However, elicitation of T cells with strong antitumor efficacy requires intricate multistep processes that have been difficult to attain with traditional vaccination approaches. Here, a multifunctional nanovaccine platform has been developed for direct delivery of neoantigens and adjuvants to lymph nodes (LNs) and highly efficient induction of neoantigen-specific T cell responses. A PEGylated reduced graphene oxide nanosheet (RGO-PEG, 20-30 nm in diameter) is a highly modular and biodegradable platform for facile preparation of neoantigen vaccines within 2 h. RGO-PEG exhibits rapid, efficient (15-20% ID/g), and sustained (up to 72 h) accumulation in LNs, achieving >100-fold improvement in LN-targeted delivery, compared with soluble vaccines. Moreover, RGO-PEG induces intracellular reactive oxygen species in dendritic cells, guiding antigen processing and presentation to T cells. Importantly, a single injection of RGO-PEG vaccine elicits potent neoantigen-specific T cell responses lasting up to 30 days and eradicates established MC-38 colon carcinoma. Further combination with anti-PD-1 therapy achieved great therapeutic improvements against B16F10 melanoma. RGO-PEG may serve a powerful delivery platform for personalized cancer vaccination.
AB - Therapeutic cancer vaccines require robust cellular immunity for the efficient killing of tumor cells, and recent advances in neoantigen discovery may provide safe and promising targets for cancer vaccines. However, elicitation of T cells with strong antitumor efficacy requires intricate multistep processes that have been difficult to attain with traditional vaccination approaches. Here, a multifunctional nanovaccine platform has been developed for direct delivery of neoantigens and adjuvants to lymph nodes (LNs) and highly efficient induction of neoantigen-specific T cell responses. A PEGylated reduced graphene oxide nanosheet (RGO-PEG, 20-30 nm in diameter) is a highly modular and biodegradable platform for facile preparation of neoantigen vaccines within 2 h. RGO-PEG exhibits rapid, efficient (15-20% ID/g), and sustained (up to 72 h) accumulation in LNs, achieving >100-fold improvement in LN-targeted delivery, compared with soluble vaccines. Moreover, RGO-PEG induces intracellular reactive oxygen species in dendritic cells, guiding antigen processing and presentation to T cells. Importantly, a single injection of RGO-PEG vaccine elicits potent neoantigen-specific T cell responses lasting up to 30 days and eradicates established MC-38 colon carcinoma. Further combination with anti-PD-1 therapy achieved great therapeutic improvements against B16F10 melanoma. RGO-PEG may serve a powerful delivery platform for personalized cancer vaccination.
KW - Cancer immunotherapy
KW - Cancer vaccine
KW - Nanosheet
KW - Positron emission tomography
KW - Reduced graphene oxide
UR - http://www.scopus.com/inward/record.url?scp=85094559738&partnerID=8YFLogxK
U2 - 10.1021/acsnano.0c05062
DO - 10.1021/acsnano.0c05062
M3 - Article
C2 - 32902245
AN - SCOPUS:85094559738
SN - 1936-0851
VL - 14
SP - 13268
EP - 13278
JO - ACS Nano
JF - ACS Nano
IS - 10
ER -