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FAP‐Targeted Photodynamic Therapy Mediated by Ferritin Nanoparticles Elicits an Immune Response against Cancer Cells and Cancer Associated Fibroblasts
Author(s) -
Zhou Shiyi,
Zhen Zipeng,
Paschall Amy V.,
Xue Lijun,
Yang Xueyuan,
Bebin Blackwell AnneGaelle,
Cao Zhengwei,
Zhang Weizhong,
Wang Mengzhe,
Teng Yong,
Zhou Gang,
Li Zibo,
Avci Fikri Y.,
Tang Wei,
Xie Jin
Publication year - 2021
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.202007017
Subject(s) - fibroblast activation protein, alpha , cancer associated fibroblasts , cancer research , cancer , photodynamic therapy , tumor microenvironment , immune system , cancer cell , antibody , immunosuppression , immunotherapy , adoptive cell transfer , medicine , abscopal effect , immunology , t cell , chemistry , organic chemistry
Abstract 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 ZnF 16 Pc‐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.