경북의대 / 전인선, 유재도, 김소연*
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.
Affiliations
In Seon Jeon 1 , Jae Do Yoo 1 , Smriti Gurung 2 , Minseong Kim 1 , Chanju Lee 3 , Eun Jung Park 3 , Rang-Woon Park 1 , Byungheon Lee 1 , Soyoun Kim 4
1 Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu, 41944, Republic of Korea; BK21 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; CMRI, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu, 41944, Republic of Korea.
2 Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu, 41944, Republic of Korea; BK21 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.
3 Cancer Immunology Branch, Division of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, 10408, Republic of Korea.
4 Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu, 41944, Republic of Korea; CMRI, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu, 41944, Republic of Korea. Electronic address: soyounki@knu.ac.kr.
편집위원
최근 종양면역치료제 연구의 큰 흐름은 PD-L1(programmed cell death 1 ligand 1), PD-1(programmed cell death 1) 연구이다. 이는 항체를 이용하는 것이기 때문에 큰 비용 및 간혹 부작용이 있을 수 있다. 이러한 아쉬운 점을 극복하기 위해 연구진은 나노입자 기반의 몇 가지 종양면역치료제 PD-L1pep1-ferritin nanocage를 개발하였다. 이 나노케이지들은 형광염료를 표지하여 생체분자영상을 진행할 수 있었고, 나노케이지의 특성상 Dox같은 항암제까지 주입할 수 있기에 종양면역치료제로써의 가능성을 보여주었다.
2021-05-06 15:51:45