DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, Dasom | ko |
dc.contributor.author | Park, Jin-Ho | ko |
dc.contributor.author | Kim, Tae-Yoon | ko |
dc.contributor.author | Kim, Dong-Gun | ko |
dc.contributor.author | Byun, June-Ho | ko |
dc.contributor.author | Kim, Hak-Sung | ko |
dc.date.accessioned | 2022-12-23T09:00:29Z | - |
dc.date.available | 2022-12-23T09:00:29Z | - |
dc.date.created | 2022-12-23 | - |
dc.date.created | 2022-12-23 | - |
dc.date.created | 2022-12-23 | - |
dc.date.issued | 2022-09 | - |
dc.identifier.citation | INTERNATIONAL JOURNAL OF PHARMACEUTICS, v.625 | - |
dc.identifier.issn | 0378-5173 | - |
dc.identifier.uri | http://hdl.handle.net/10203/303668 | - |
dc.description.abstract | Human interleukin-15 (hIL-15) has attracted a considerable attention as a promising cancer immunotherapeutic due to its function to directly stimulate the proliferation and cytotoxic activity of NK and T cells. Nevertheless, a relatively short half-life of hIL-15 requires repeated administration and higher doses, causing serious side effects. Here, we demonstrate an enhanced blood half-life and biological activity of hIL-15 through genetic fusion of a human serum albumin-specific protein binder (rHSA). The fusion construct (rHSA-IL15) was observed to maintain respective binding activities for both hIL-15 receptor α and human serum albumin. The rHSA-IL15 led to a significant increase in the secretion of Granzyme B and INF-γ by immune cells compare to free hIL-15, expanding the population of activated T cell subset such as CD4 + T and CD8+ T cells. The terminal half-life of the rHSA-IL15 was prolonged by around a 40-fold in transgenic mice expressing human serum albumin, compared to free hIL-15. The rHSA-IL15 resulted in distinct anti-tumor activities in xenograft SCC (squamous cell carcinoma) mouse and allograft melanoma mouse models through activation of NK and CD8+ T cells. The rHSA-IL15 is expected to be used in cancer immunotherapy, assisting in the development of other cytokines as immunotherapeutic agents with greater efficacy. © 2022 Elsevier B.V. | - |
dc.language | English | - |
dc.publisher | ELSEVIER | - |
dc.title | Enhanced half-life and antitumor activity of interleukin-15 through genetic fusion of a serum albumin-specific protein binder | - |
dc.type | Article | - |
dc.identifier.wosid | 000891282900009 | - |
dc.identifier.scopusid | 2-s2.0-85135291894 | - |
dc.type.rims | ART | - |
dc.citation.volume | 625 | - |
dc.citation.publicationname | INTERNATIONAL JOURNAL OF PHARMACEUTICS | - |
dc.identifier.doi | 10.1016/j.ijpharm.2022.122059 | - |
dc.contributor.localauthor | Kim, Hak-Sung | - |
dc.contributor.nonIdAuthor | Park, Jin-Ho | - |
dc.contributor.nonIdAuthor | Byun, June-Ho | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | Genetic fusion | - |
dc.subject.keywordAuthor | Half-life | - |
dc.subject.keywordAuthor | Immune cells | - |
dc.subject.keywordAuthor | Immunotherapy | - |
dc.subject.keywordAuthor | Interleukin 15 | - |
dc.subject.keywordAuthor | Protein binder | - |
dc.subject.keywordPlus | ALPHA-CHAIN | - |
dc.subject.keywordPlus | IL-15 | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordPlus | IMMUNOTHERAPY | - |
dc.subject.keywordPlus | CYTOKINES | - |
dc.subject.keywordPlus | COMPLEX | - |
dc.subject.keywordPlus | NK | - |
dc.subject.keywordPlus | LYMPHOCYTES | - |
dc.subject.keywordPlus | HOMEOSTASIS | - |
dc.subject.keywordPlus | RECEPTORS | - |
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