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Biomaterials, Available online 22 January 2021, 120685 | https://doi.org/10.1016/j.biomaterials.2021.120685 Anticancer nanocage platforms for combined immunotherapy designed to harness immune checkpoints and deliver anticancer drugs

In Seon Jeon^a,b,c,1, Jae Do Yoo^a,b,c,1, Smriti Gurung^a,b, Minseong Kim^a,b,c, Chanju Lee^d, Eun Jung Park^d, Rang-Woon Park^a,b,c, Byungheon Lee^a,b,c, Soyoun Kim^a,c,*

^aDepartment of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu 41944, Republic of Korea
^bBK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu 41944, Republic of Korea
^cCMRI, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu 41944, Republic of Korea
^dCancer Immunology Branch, Division of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, 10408, Republic of Korea

¹These authors contributed equally.

^*Corresponding author

Abstract

The interaction of programmed cell death 1 ligand 1 (PD-L1) with its receptor, programmed cell death 1 (PD-1), inhibits T cell responses. Monoclonal antibodies that block this interaction have been shown effective as immunotherapy. However, only a subset of cancers exhibits a durable response to PD-1/PD-L1 blockade. Moreover, antibody-based immune checkpoint blockade is costly and is occasionally accompanied by systemic side effects. To overcome these limitations of antibody-based immune checkpoint blockade, an immune checkpoint-blocking ferritin nanocage displaying 24 PD-L1 binding peptides (PD-L1pep1) on its surface was designed and constructed. These ferritin nanocages displaying PD-L1pep1 (PpNF) specifically bind to PD-L1 expressed on cancer cells or to purified PD-L1 with a ∼30 nM binding affinity. The addition of PpNF to co-cultures of T cells and cancer cells inhibited PD-1/PD-L1 interactions and restored T cell activities. In a mouse model of syngeneic colon cancer, PpNF specifically targeted tumors and showed antitumor activity. Moreover, PpNF nanocages encapsulating the chemotherapeutic drug doxorubicin had more potent antitumor activity than a monoclonal antibody against PD-L1. These results demonstrate that ferritin nanocages displaying surface PD-L1pep1 can be efficiently applied for immunotherapy, especially when encapsulating small chemotherapeutic drugs. These nanocages may have promise as an immunotherapeutic nanomedicine against various solid tumors.

Keywords : PD-L1 binding peptide, immune checkpoint, ferritin, immunotherapy, combination therapy, doxorubicin

논문정보

형식Research article
게재일2021년 01월 (BRIC 등록일 2021-01-27)
연구진국내 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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