Selective targeting of engineered T cells using orthogonal IL-2 cytokine-receptor complexes
| Autor: | Indigo Chris King, Akanksha Chhabra, David Baker, Leah V. Sibener, Matthew Tiffany, Antoni Ribas, Alan C. Le, Jeffrey A. Bluestone, Leon Su, Stephanie L. Silveria, Benson M. George, Eleonora Trotta, Jonathan T. Sockolosky, Giulia Parisi, Kevin Jude, Judith A. Shizuru, K. Christopher Garcia, Lora Picton |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes General Science & Technology medicine.medical_treatment T cell T-Lymphocytes Adoptive Melanoma Experimental Bioengineering CD8-Positive T-Lymphocytes Immunotherapy Adoptive Article Cell therapy Vaccine Related 03 medical and health sciences Mice Experimental 0302 clinical medicine Immune system Neoplasms Receptors medicine Animals Humans Melanoma Cell Engineering Cancer Multidisciplinary 5.2 Cellular and gene therapies Chemistry HEK 293 cells Cell Membrane Receptors Interleukin-2 Immunotherapy Cell biology 030104 developmental biology Cytokine medicine.anatomical_structure HEK293 Cells 5.1 Pharmaceuticals 030220 oncology & carcinogenesis Cytokines Interleukin-2 Immunization Development of treatments and therapeutic interventions Cytokine receptor CD8 Biotechnology |
| Zdroj: | Science (New York, N.Y.), vol 359, iss 6379 Sockolosky, JT; Trotta, E; Parisi, G; Picton, L; Su, LL; Le, AC; et al.(2018). Selective targeting of engineered T cells using orthogonal IL-2 cytokine-receptor complexes. SCIENCE, 359(6379), 1037-+. doi: 10.1126/science.aar3246. UCLA: Retrieved from: http://www.escholarship.org/uc/item/1fn5n8p9 |
| DOI: | 10.1126/science.aar3246. |
| Popis: | Engineering cytokine-receptor pairs Interleukin-2 (IL-2) is an important cytokine that helps T cells destroy tumors and virus-infected cells. IL-2 has great therapeutic promise but is limited by toxic side effects and its capacity to both activate and repress immune responses. Sockolosky et al. set out to improve IL-2–based immunotherapy by engineering synthetic IL-2–receptor pairs (i.e., IL-2 and its receptor, IL-2R) (see the Perspective by Mackall). Engineered complexes transmitted IL-2 signals but only interacted with each other and not with endogenous IL-2/IL-2R. Treatment of mice with IL-2 improved the ability of engineered T cells to reject tumors with no obvious side effects. This type of approach may provide a way to mitigate toxicities associated with some cytokine-based immunotherapies. Science , this issue p. 1037 ; see also p. 990 |
| Databáze: | OpenAIRE |
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