한빛사논문
- 조회526
Dahong Kim1,2, Seona Jo3,4, Dongjin Lee1, Seok‑Min Kim3,4, Ji Min Seok1,2, Seon Ju Yeo1, Jun Hee Lee1, Jae Jong Lee1, Kangwon Lee2,5, Tae‑Don Kim3,4,6,7*† and Su A Park1*†
1Nano Convergence & Manufacturing Systems, Korea Institute of Machinery and Materials (KIMM), Daejeon 34103, Republic of Korea.
2Department of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea.
3Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
4Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon 34113, Republic of Korea.
5Research Institute for Convergence Science, Seoul National University, Seoul 08826, Republic of Korea.
6Biomedical Mathematics Group, Institute for Basic Science, Daejeon 34126, Republic of Korea.
7Department of Biopharmaceutical Convergence, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
†Tae-Don Kim and Su A Park are corresponding authors equally contributed this work.
*Correspondence: Tae‑Don Kim, Su A Park
Abstract
Background: Patients face a serious threat if a solid tumor leaves behind partial residuals or cannot be completely removed after surgical resection. Immunotherapy has attracted attention as a method to prevent this condition. However, the conventional immunotherapy method targeting solid tumors, that is, intravenous injection, has limitations in homing in on the tumor and in vivo expansion and has not shown effective clinical results.
Method: To overcome these limitations, NK cells (Natural killer cells) were encapsulated in micro/macropore-forming hydrogels using 3D bioprinting to target solid tumors. Sodium alginate and gelatin were used to prepare micro-macroporous hydrogels. The gelatin contained in the alginate hydrogel was removed because of the thermal sensitivity of the gelatin, which can generate interconnected micropores where the gelatin was released. Therefore, macropores can be formed through bioprinting and micropores can be formed using thermally sensitive gelatin to make macroporous hydrogels.
Results: It was confirmed that intentionally formed micropores could help NK cells to aggregate easily, which enhances cell viability, lysis activity, and cytokine release. Macropores can be formed using 3D bioprinting, which enables NK cells to receive the essential elements. We also characterized the functionality of NK 92 and zEGFR-CAR-NK cells in the pore-forming hydrogel. The antitumor effects on leukemia and solid tumors were investigated using an in vitro model.
Conclusion: We demonstrated that the hydrogel encapsulating NK cells created an appropriate micro-macro environment for clinical applications of NK cell therapy for both leukemia and solid tumors via 3D bioprinting. 3D bioprinting makes macro-scale clinical applications possible, and the automatic process shows potential for development as an off-the-shelf immunotherapy product. This immunotherapy system could provide a clinical option for preventing tumor relapse and metastasis after tumor resection. Micro/macropore-forming hydrogel with NK cells fabricated by 3D bioprinting and implanted into the tumor site.
논문정보
- Research article
- 2023년 06월 (BRIC 등록일 2023-07-04)
- 국내 연구진
- 생명과학 > 면역학
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