TY - JOUR
T1 - Systemic tumour suppression via the preferential accumulation of erythrocyte-anchored chemokine-encapsulating nanoparticles in lung metastases
AU - Zhao, Zongmin
AU - Ukidve, Anvay
AU - Krishnan, Vinu
AU - Fehnel, Alexandra
AU - Pan, Daniel C.
AU - Gao, Yongsheng
AU - Kim, Jayoung
AU - Evans, Michael A.
AU - Mandal, Abhirup
AU - Guo, Junling
AU - Muzykantov, Vladimir R.
AU - Mitragotri, Samir
N1 - Funding Information:
We thank D. Mooney for guidance. This work was financially supported by the Wyss Institute at Harvard University. The authors acknowledge funding from the National Institutes of Health (grant no. 1R01HL143806-01).
Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2021/5
Y1 - 2021/5
N2 - Eliciting immune responses against primary tumours is hampered by their immunosuppressive microenvironment and by the greater inaccessibility of deeper intratumoural cells. However, metastatic tumour cells are exposed to highly perfused and immunoactive organs, such as the lungs. Here, by taking advantage of the preferential colocalization of intravenously administered erythrocytes with metastases in the lungs, we show that treatment with chemokine-encapsulating nanoparticles that are non-covalently anchored onto the surface of injected erythrocytes results in local and systemic tumour suppression in mouse models of lung metastasis. Such erythrocyte-anchored systemic immunotherapy led to the infiltration of effector immune cells into the lungs, in situ immunization without the need for exogenous antigens, inhibition of the progression of lung metastasis, and significantly extended animal survival and systemic immunity that suppressed the growth of distant tumours after rechallenge. Erythrocyte-mediated systemic immunotherapy may represent a general and potent strategy for cancer vaccination.
AB - Eliciting immune responses against primary tumours is hampered by their immunosuppressive microenvironment and by the greater inaccessibility of deeper intratumoural cells. However, metastatic tumour cells are exposed to highly perfused and immunoactive organs, such as the lungs. Here, by taking advantage of the preferential colocalization of intravenously administered erythrocytes with metastases in the lungs, we show that treatment with chemokine-encapsulating nanoparticles that are non-covalently anchored onto the surface of injected erythrocytes results in local and systemic tumour suppression in mouse models of lung metastasis. Such erythrocyte-anchored systemic immunotherapy led to the infiltration of effector immune cells into the lungs, in situ immunization without the need for exogenous antigens, inhibition of the progression of lung metastasis, and significantly extended animal survival and systemic immunity that suppressed the growth of distant tumours after rechallenge. Erythrocyte-mediated systemic immunotherapy may represent a general and potent strategy for cancer vaccination.
UR - http://www.scopus.com/inward/record.url?scp=85096076472&partnerID=8YFLogxK
U2 - 10.1038/s41551-020-00644-2
DO - 10.1038/s41551-020-00644-2
M3 - Article
C2 - 33199847
AN - SCOPUS:85096076472
SN - 2157-846X
VL - 5
SP - 441
EP - 454
JO - Nature Biomedical Engineering
JF - Nature Biomedical Engineering
IS - 5
ER -