Eun Young Jeon1, Da-som Choi2, Seunghyun Choi3,4, Ju-young Won2, Yunju Jo3,4, Hye-bin Kim2, Youngmee Jung1,5,6, Sang Chul Shin7, Hophil Min8, Hae Woong Choi4, Myeong Sup Lee9, Yoon Park3, Justin J. Chung10,11, Hyung-seung Jin2
1Center for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, South Korea
2Department of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
3Theragnosis Center, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, South Korea
4Department of Life Sciences, Korea University, Seoul, South Korea
5School of Electrical and Electronic Engineering, Yonsei University, Seoul, South Korea
6Yonsei-KIST Convergence Research Institute, Seoul, South Korea
7Technology Support Center, Korea Institute of Science and Technology (KIST), Seoul, South Korea
8Doping Control Center, Korea Institute of Science and Technology (KIST), Seoul, South Korea
9Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, South Korea
10Transdisciplinary Department of Medicine and Advanced Technology, Seoul National University Hospital, Seoul, South Korea
11Department of Medicine, Seoul National University College of Medicine, Seoul, South Korea
Eun Young Jeon and Da-som Choi contributed equally to this study.
CORRESPONDING AUTHORS : Yoon Park, Justin J. Chung, Hyung-Seung Jin
Adoptive cell therapy (ACT) with antigen-specific T cells is a promising treatment approach for solid cancers. Interleukin-2 (IL-2) has been utilized in boosting the efficacy of ACT. However, the clinical applications of IL-2 in combination with ACT is greatly limited by short exposure and high toxicities. Herein, a complex coacervate was designed to intratumorally deliver IL-2 in a sustained manner and protect against proteolysis. The complex coacervate consisted of fucoidan, a specific IL-2 binding glycosaminoglycan, and poly-l-lysine, a cationic counterpart (FPC2). IL-2-laden FPC2 exhibited a preferential bioactivity in ex vivo expansion of CD8+T cells over Treg cells. Additionally, FPC2 was embedded in pH modulating injectable gel (FPC2-IG) to endure the acidic tumor microenvironment. A single intratumoral administration of FPC2-IG-IL-2 increased expansion of tumor-infiltrating cytotoxic lymphocytes and reduced frequencies of myeloid populations. Notably, the activation and persistency of tumor-reactive T cells were observed only in the tumor site, not in the spleen, confirming a localized effect of FPC2-IG-IL-2. The immune-favorable tumor microenvironment induced by FPC2-IG-IL-2 enabled adoptively transferred TCR-engineered T cells to effectively eradicate tumors. FPC2-IG delivery system is a promising strategy for T-cell-based immunotherapies.