Jeon, Eun Young Choi, Da-som Choi, Seunghyun Won, Ju-young Jo, Yunju Kim, Hye-bin Jung, Youngmee Shin, Sang Chul Min, Hophil Choi, Hae Woong Lee, Myeong Sup Park, Yoon Chung, Justin J. Jin, Hyung-seung 2024-01-19T10:32:02Z 2024-01-19T10:32:02Z 2022-07-14 2023-01 2380-6761 https://pubs.kist.re.kr/handle/201004/114192 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. English Wiley | American Institute of Chemical Engineers; Society for Biological Engineering Enhancing adoptive T-cell therapy with fucoidan-based IL-2 delivery microcapsules Article 10.1002/btm2.10362 1 Bioengineering & Translational Medicine, v.8, no.1 Bioengineering & Translational Medicine 8 1 N scie scopus 000820667200001 Biotechnology & Applied Microbiology Engineering, Biomedical Pharmacology & Pharmacy Biotechnology & Applied Microbiology Engineering Pharmacology & Pharmacy Article CANCER IMMUNOTHERAPY HEPARIN BINDING adoptive T-cell therapy complex coacervate fucoidan immunotherapy interleukin-2