Targeting CAMKII to reprogram tumor-associated macrophages and inhibit tumor cells for cancer immunotherapy with an injectable hybrid peptide hydrogel
Identifieur interne : 000037 ( Main/Merge ); précédent : 000036; suivant : 000038Targeting CAMKII to reprogram tumor-associated macrophages and inhibit tumor cells for cancer immunotherapy with an injectable hybrid peptide hydrogel
Auteurs : Xiaomeng Dai [République populaire de Chine] ; Jingshu Meng [République populaire de Chine] ; Suke Deng [République populaire de Chine] ; Lingling Zhang [République populaire de Chine] ; Chao Wan [République populaire de Chine] ; Lisen Lu [République populaire de Chine] ; Jing Huang [République populaire de Chine] ; Yan Hu [République populaire de Chine] ; Zhanjie Zhang [République populaire de Chine] ; Yan Li [République populaire de Chine] ; Jonathan F. Lovell [États-Unis] ; Gang Wu [République populaire de Chine] ; Kunyu Yang [République populaire de Chine] ; Honglin Jin [République populaire de Chine]Source :
- Theranostics [ 1838-7640 ] ; 2020.
Abstract
Simultaneously targeted treatment of tumor cells and their surrounding growth-supporting immune cells is a promising strategy to reshape immunosuppressive tumor microenvironment (TME) and potentiate host innate and adaptive antitumor immune responses.
Url:
DOI: 10.7150/thno.42385
PubMed: 32194854
PubMed Central: 7053188
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PMC:7053188Le document en format XML
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<author><name sortKey="Dai, Xiaomeng" sort="Dai, Xiaomeng" uniqKey="Dai X" first="Xiaomeng" last="Dai">Xiaomeng Dai</name>
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<author><name sortKey="Meng, Jingshu" sort="Meng, Jingshu" uniqKey="Meng J" first="Jingshu" last="Meng">Jingshu Meng</name>
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<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
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<author><name sortKey="Lu, Lisen" sort="Lu, Lisen" uniqKey="Lu L" first="Lisen" last="Lu">Lisen Lu</name>
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<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
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<author><name sortKey="Huang, Jing" sort="Huang, Jing" uniqKey="Huang J" first="Jing" last="Huang">Jing Huang</name>
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<country xml:lang="fr">République populaire de Chine</country>
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<placeName><settlement type="city">Wuhan</settlement>
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<author><name sortKey="Hu, Yan" sort="Hu, Yan" uniqKey="Hu Y" first="Yan" last="Hu">Yan Hu</name>
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<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
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<author><name sortKey="Zhang, Zhanjie" sort="Zhang, Zhanjie" uniqKey="Zhang Z" first="Zhanjie" last="Zhang">Zhanjie Zhang</name>
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<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
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<author><name sortKey="Li, Yan" sort="Li, Yan" uniqKey="Li Y" first="Yan" last="Li">Yan Li</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
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<author><name sortKey="Lovell, Jonathan F" sort="Lovell, Jonathan F" uniqKey="Lovell J" first="Jonathan F." last="Lovell">Jonathan F. Lovell</name>
<affiliation wicri:level="4"><nlm:aff id="A2">Department of Chemical and Biological Engineering, University at Buffalo, State University of New York. Buffalo, New York 14260, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Chemical and Biological Engineering, University at Buffalo, State University of New York. Buffalo, New York 14260</wicri:regionArea>
<orgName type="university">Université d'État de New York à Buffalo</orgName>
<placeName><settlement type="city">Buffalo (New York)</settlement>
<region type="state">État de New York</region>
</placeName>
</affiliation>
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<author><name sortKey="Wu, Gang" sort="Wu, Gang" uniqKey="Wu G" first="Gang" last="Wu">Gang Wu</name>
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<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
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<author><name sortKey="Yang, Kunyu" sort="Yang, Kunyu" uniqKey="Yang K" first="Kunyu" last="Yang">Kunyu Yang</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Jin, Honglin" sort="Jin, Honglin" uniqKey="Jin H" first="Honglin" last="Jin">Honglin Jin</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Theranostics</title>
<idno type="eISSN">1838-7640</idno>
<imprint><date when="2020">2020</date>
</imprint>
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<front><div type="abstract" xml:lang="en"><p>Simultaneously targeted treatment of tumor cells and their surrounding growth-supporting immune cells is a promising strategy to reshape immunosuppressive tumor microenvironment (TME) and potentiate host innate and adaptive antitumor immune responses.</p>
<p><bold>Methods</bold>
: We designed a series of melittin-(RADA)<sub>n</sub>
hybrid peptide sequences with varying self-assembling motifs of RADA and screened out a melittin-(RADA)<sub>6</sub>
peptide that has an optimal gel-formation ability and <italic>in vitro</italic>
antitumor activity.</p>
<p><bold>Results</bold>
: The formed melittin-(RADA)<sub>6</sub>
(MR<sub>52</sub>
) hydrogel scaffold could be loaded with a specific Ca<sup>2+</sup>
/calmodulin-dependent protein kinase II (CAMKII) inhibitor, KN93, originally found to have both direct tumoricidal activity and macrophages-reprogramming ability, for potent immunotherapy against melanoma and hepatoma ascites in mice models. Our MR<sub>52</sub>
hydrogel has an interweaving nanofiber-like structure, possesses direct antitumor and controlled drug release properties<italic>,</italic>
and promotes the enhanced intracellular uptake of loaded cargo. Compared to free KN93, the MR<sub>52</sub>
-KN93 hydrogel (MRK) improved the killing effects and levels of immunogenic cell death (ICD) on tumor cells significantly. Due to the dual role of KN93, the injection of the MRK hydrogel retarded the growth of subcutaneous melanoma tumors dramatically and resulted in a high number of mature dendritic cells of draining lymph nodes, significantly enhancing the portion of cytotoxic T cells and reduced number of M2-like tumor-associated macrophages (TAMs) in tumors. Using a mouse model of malignant ascites (MAs), where traditional therapy was ineffective, we demonstrated that the MRK hydrogel treatment offered a significantly prolonged survival compared to controls. Following treatment with the MRK hydrogel, macrophages had elevated programmed cell death protein ligand-1 (PD-L1) expression, promising follow-up combined anti-PD-1 therapy that confers a cure rate of approximately 30% against MAs in mice models.</p>
<p><bold>Conclusion</bold>
: Thus, the MRK hydrogel may serve as a prospective platform for antitumor applications.</p>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Holzel, M" uniqKey="Holzel M">M Holzel</name>
</author>
<author><name sortKey="Bovier, A" uniqKey="Bovier A">A Bovier</name>
</author>
<author><name sortKey="Tuting, T" uniqKey="Tuting T">T Tuting</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zou, W" uniqKey="Zou W">W Zou</name>
</author>
</analytic>
</biblStruct>
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