Development of an attenuated interleukin-2 cytokine fusion protein that can be activated by tumor expressed matrix metalloproteinases (165.19)
| العنوان: | Development of an attenuated interleukin-2 cytokine fusion protein that can be activated by tumor expressed matrix metalloproteinases (165.19) |
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| المؤلفون: | Denise Skrombolas, John Puskas, Abigail Sedlacek, Edith Lord, John Frelinger |
| المصدر: | The Journal of Immunology. 186:165.19-165.19 |
| بيانات النشر: | The American Association of Immunologists, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Immunology, Immunology and Allergy |
| الوصف: | Cytokines have been used to treat tumors, however, side effects often limit their use when delivered systemically. We set out to develop an approach in which cytokines would be preferentially activated at the site of growing tumors. We have constructed a novel fusion protein (FP) consisting of the cytokine interleukin-2 (IL-2) joined to a specific inhibitor moiety, the interleukin-2 receptor alpha chain separated by a protease cleavage sequence recognized by matrix metalloproteinases (MMPs). The rationale is that the cytokine would be relatively inactive in the intact fusion protein but its biological activity would increase after protease cleavage. We analyzed a baculovirus expressed FP biochemically by immunoblot analyses and functionally using the IL-2 dependent CTLL-2 cell line. IL-2 activity is attenuated over 50 fold in the intact FP compared to the same molar amount of IL-2. MMP cleavage releases IL-2 resulting in an increase in the amount of biologically available IL-2. Additionally, the FP showed efficacy in vivo using a peritoneal tumor model employing Colon 38. This general approach may be applicable to other cytokines as well as other proteases. |
| تدمد: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.186.supp.165.19 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::1cb6a081d6ad9000981ba6c0c731e305 https://doi.org/10.4049/jimmunol.186.supp.165.19 |
| رقم الانضمام: | edsair.doi...........1cb6a081d6ad9000981ba6c0c731e305 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
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| DOI: | 10.4049/jimmunol.186.supp.165.19 |