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 - 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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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 -