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Enhanced Natural Killer Cell Immunotherapy by Rationally Assembling Fc Fragments of Antibodies onto Tumor Membranes
Author(s) -
Ji Tianjiao,
Lang Jiayan,
Ning Bo,
Qi Feifei,
Wang Hui,
Zhang Yinlong,
Zhao Ruifang,
Yang Xiao,
Zhang Lijing,
Li Wei,
Shi Xinghua,
Qin Zhihai,
Zhao Ying,
Nie Guangjun
Publication year - 2019
Publication title -
advanced materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 10.707
H-Index - 527
eISSN - 1521-4095
pISSN - 0935-9648
DOI - 10.1002/adma.201804395
Subject(s) - antibody dependent cell mediated cytotoxicity , immunotherapy , antigen , monoclonal antibody , antibody , cancer research , cancer immunotherapy , tumor microenvironment , biology , materials science , immunology , immune system , tumor cells
Recent advances in cancer immunotherapy have exploited the efficient potential of natural killer (NK) cells to kill tumor cells through antibody‐dependent cell‐mediated cytotoxicity (ADCC). However, this therapeutic strategy is seriously limited by tumor antigen heterogeneity since antibodies can only recognize specific antigens. In this work, modified antibodies or their Fc fragments that can target solid tumors without the necessity of specific antigen presentation on tumors are developed. Briefly, Fc fragments or therapeutic monoclonal antibodies are conjugated with the N‐terminus of pH low insertion peptide so that they will selectively assemble onto the membrane of solid tumor cells via the conformational transformation of the peptide by responding to the acidic tumor microenvironment. The inserted Fc fragments or antibodies can efficiently activate NK cells, initiating ADCC and killing multiple types of tumor cells, including antigen‐negative cancer cells. In vivo therapeutic results also exhibit significant efficacy on both primary solid tumors and tumor metastasis. These modified Fc fragments and antibodies present strong potential to overcome the limitation of tumor antigen heterogeneity, broadening the applications of NK cell immunotherapy on solid tumor treatment.