TY - JOUR
T1 - FAP-Targeted Photodynamic Therapy Mediated by Ferritin Nanoparticles Elicits an Immune Response against Cancer Cells and Cancer Associated Fibroblasts
AU - Zhou, Shiyi
AU - Zhen, Zipeng
AU - Paschall, Amy V.
AU - Xue, Lijun
AU - Yang, Xueyuan
AU - Bebin Blackwell, Anne Gaelle
AU - Cao, Zhengwei
AU - Zhang, Weizhong
AU - Wang, Mengzhe
AU - Teng, Yong
AU - Zhou, Gang
AU - Li, Zibo
AU - Avci, Fikri Y.
AU - Tang, Wei
AU - Xie, Jin
N1 - Funding Information:
The authors would like to thank Julie Nelson in CTEGD Cytometry Shared Resource Laboratory at University of Georgia (UGA) for help with troubleshooting in flow studies. The authors also appreciate Dr. Ted Ross at Center for Vaccines and Immunology of UGA helping with ELISpot reader. The authors appreciate the support by the National Science Foundation (CAREER grant no. NSF1552617 to J.X.), and the National Institute of Biomedical Imaging and Bioengineering (grant no. R01EB022596 to J.X.). This work was also supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award number UL1TR002378. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Funding Information:
The authors would like to thank Julie Nelson in CTEGD Cytometry Shared Resource Laboratory at University of Georgia (UGA) for help with troubleshooting in flow studies. The authors also appreciate Dr. Ted Ross at Center for Vaccines and Immunology of UGA helping with ELISpot reader. The authors appreciate the support by the National Science Foundation (CAREER grant no. NSF1552617 to J.X.), and the National Institute of Biomedical Imaging and Bioengineering (grant no. R01EB022596 to J.X.). This work was also supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award number UL1TR002378. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2020 Wiley-VCH GmbH
PY - 2021/2/10
Y1 - 2021/2/10
N2 - Cancer-associated fibroblasts (CAFs) are present in many types of tumors and play a pivotal role in tumor progression and immunosuppression. Fibroblast-activation protein (FAP), which is overexpressed on CAFs, has been indicated as a universal tumor target. However, FAP expression is not restricted to tumors, and systemic treatment against FAP often causes severe side effects. To solve this problem, a photodynamic therapy (PDT) approach is developed based on ZnF16Pc-loaded and FAP-specific single chain variable fragment (scFv)-conjugated apoferritin nanoparticles, or αFAP-Z@FRT. αFAP-Z@FRT PDT efficiently eradicates CAFs in tumors without inducing systemic toxicity. When tested in murine 4T1 models, the treatment elicits anti-cancer immunity, causing suppression of both primary and distant tumors, that is, the abscopal effect. Treatment efficacy is enhanced when αFAP-Z@FRT PDT is used in combination with anti-PD1 antibodies. Interestingly, it is found that the PDT treatment not only elicits a cellular immunity against cancer cells, but also stimulates an anti-CAFs immunity. This is supported by an adoptive cell transfer study, where T cells taken from 4T1-tumor-bearing animals treated with αFAP PDT retard the growth of A549 tumors established on nude mice. Overall, this approach is unique for permitting site-specific eradication of CAFs and inducing a broad spectrum anti-cancer immunity.
AB - Cancer-associated fibroblasts (CAFs) are present in many types of tumors and play a pivotal role in tumor progression and immunosuppression. Fibroblast-activation protein (FAP), which is overexpressed on CAFs, has been indicated as a universal tumor target. However, FAP expression is not restricted to tumors, and systemic treatment against FAP often causes severe side effects. To solve this problem, a photodynamic therapy (PDT) approach is developed based on ZnF16Pc-loaded and FAP-specific single chain variable fragment (scFv)-conjugated apoferritin nanoparticles, or αFAP-Z@FRT. αFAP-Z@FRT PDT efficiently eradicates CAFs in tumors without inducing systemic toxicity. When tested in murine 4T1 models, the treatment elicits anti-cancer immunity, causing suppression of both primary and distant tumors, that is, the abscopal effect. Treatment efficacy is enhanced when αFAP-Z@FRT PDT is used in combination with anti-PD1 antibodies. Interestingly, it is found that the PDT treatment not only elicits a cellular immunity against cancer cells, but also stimulates an anti-CAFs immunity. This is supported by an adoptive cell transfer study, where T cells taken from 4T1-tumor-bearing animals treated with αFAP PDT retard the growth of A549 tumors established on nude mice. Overall, this approach is unique for permitting site-specific eradication of CAFs and inducing a broad spectrum anti-cancer immunity.
KW - cancer associated fibroblast
KW - fibroblast activation protein
KW - immunomodulation
KW - immunotherapy
KW - photodynamic therapy
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UR - http://www.scopus.com/inward/citedby.url?scp=85096654149&partnerID=8YFLogxK
U2 - 10.1002/adfm.202007017
DO - 10.1002/adfm.202007017
M3 - Article
AN - SCOPUS:85096654149
SN - 1616-301X
VL - 31
JO - Advanced Functional Materials
JF - Advanced Functional Materials
IS - 7
M1 - 2007017
ER -
