A novel membrane-bound interleukin-2 promotes NK-92 cell persistence and anti-tumor activity
| Autor: | Qi Xiong, Hantao Zhang, Xuanle Ji, Yong Zhang, Gang Shi, Lei Dai, Fuyi Cheng, Huiling Wang, Jieyan Luo, Jia Xu, Yanhong Ji, Xiaolan Su, Weixiao Yang, Lin Zhang, Hongxin Deng |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | OncoImmunology, Vol 11, Iss 1 (2022) |
| Druh dokumentu: | article |
| ISSN: | 2162402X 2162-402X |
| DOI: | 10.1080/2162402X.2022.2127282 |
| Popis: | A major challenge in natural killer (NK) cell immunotherapy is the limited persistence of NK cells in vivo. However, the proliferation of NK cells is dependent on cytokines such as interleukin-2 (IL-2). Although IL-2 is a critical cytokine for NK cell activation and survival, IL-2 administration in adoptive NK cell therapy can induce adverse toxicities. To improve the persistence of NK cells and attenuate the systemic toxicity of IL-2, we constructed a cell-restricted artificial IL-2, named membrane-bound IL-2 (mbIL-2), comprising human IL-2 and human IL-2Rα joined by a classic linker. We found that mbIL-2-activated NK-92 cells can survive and proliferate in vitro and in vivo, independent of exogenous IL-2, while mbIL-2-expressing NK-92 cells do not support bystander cell survival or proliferation. Additionally, mbIL-2 enhanced NK-92 cell-mediated antitumor activity by tuning the IL-2 receptor downstream signals and NK cell receptor repertoire expression. To conclude, our novel mbIL-2 improves NK-92 cell persistence and enhances NK-92 cell-mediated antitumor activity. NK-92 cells genetically modified to express the novel mbIL-2 with potential significance for clinical development. |
| Databáze: | Directory of Open Access Journals |
| Externí odkaz: |
|