Persistence of adoptively transferred T cells with a kinetically engineered IL-2 receptor agonist
| العنوان: | Persistence of adoptively transferred T cells with a kinetically engineered IL-2 receptor agonist |
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| المؤلفون: | Ruixue Zhang, Siwen Hu-Lieskovan, Felix B. Salazar, Paige Krystofinski, Anna M. Wu, Jonathan Zalevsky, Sean Mackay, Catherine S. Grasso, Alejandro J. Garcia, Antoni Ribas, Jing Zhou, Adi Diab, Chantale Bernatchez, Deborah H. Charych, Jennifer Tsoi, Cristina Puig-Saus, Begoña Comin-Anduix, Giulia Parisi, Gardenia Cheung-Lau, Richard Tavaré, Justin Saco |
| المصدر: | Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-12 (2020) Nature communications, vol 11, iss 1 |
| بيانات النشر: | Nature Publishing Group UK, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Agonist, Adoptive cell transfer, medicine.drug_class, Science, T-Lymphocytes, Melanoma, Experimental, General Physics and Astronomy, Cancer immunotherapy, Inbred C57BL, Lymphocyte Activation, General Biochemistry, Genetics and Molecular Biology, Article, Polyethylene Glycols, Vaccine Related, 03 medical and health sciences, Experimental, Mice, 0302 clinical medicine, In vivo, Receptors, medicine, Animals, Humans, IL-2 receptor, lcsh:Science, Receptor, Melanoma, Cancer, Multidisciplinary, Chemistry, Interleukins, Receptors, Interleukin-2, General Chemistry, Adoptive Transfer, 3. Good health, Mice, Inbred C57BL, 030104 developmental biology, 030220 oncology & carcinogenesis, Cancer research, Interleukin-2, lcsh:Q, Short exposure, B16 melanoma, Homing (hematopoietic) |
| الوصف: | Interleukin-2 (IL-2) is a component of most protocols of adoptive cell transfer (ACT) therapy for cancer, but is limited by short exposure and high toxicities. NKTR-214 is a kinetically-engineered IL-2 receptor βγ (IL-2Rβγ)-biased agonist consisting of IL-2 conjugated to multiple releasable polyethylene glycol chains resulting in sustained signaling through IL-2Rβγ. We report that ACT supported by NKTR-214 increases the proliferation, homing and persistence of anti-tumor T cells compared to ACT with IL-2, resulting in superior antitumor activity in a B16-F10 murine melanoma model. The use of NKTR-214 increases the number of polyfunctional T cells in murine spleens and tumors compared to IL-2, and enhances the polyfunctionality of T and NK cells in the peripheral blood of patients receiving NKTR-214 in a phase 1 trial. In conclusion, NKTR-214 may have the potential to improve the antitumor activity of ACT in humans through increased in vivo expansion and polyfunctionality of the adoptively transferred T cells. Adoptive cell transfer (ACT) of T cells for tumor treatment often requires IL-2 administration. Here, the authors show that a modified IL-2 cytokine (NKTR-214) can outperform IL-2 in a melanoma mouse model. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::15124bc14ad6c895a8059f2f1211bb3aTest http://europepmc.org/articles/PMC6994533Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....15124bc14ad6c895a8059f2f1211bb3a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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