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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Aug 07, 2019 |
| Title |
Improved expansion, functionality and tumor targeting of adoptively transferred T cells with kinetically engineered IL-2 |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The adoptive transfer of cancer-specific T cells in combination with high dose interleukin-2 (IL-2) is able to induce effective anti-tumor responses. However, tumors frequently relapse after an initial response and the known toxicities of IL-2 further limit the use of this therapy. NKTR-214 is a CD122-biased polyethylene glycol (PEG)-genetically engineered IL-2 designed to provide sustained signaling through the heterodimeric IL-2 receptor pathway (IL-2Rβγ) to preferentially activate and expand CD8 T and natural killer (NK) cells over T regulatory cells (Tregs) in the tumor. We report that combination of adoptive T cell transfer (ACT) and NKTR-214 markedly increases the proliferation, homing and polyfunctionality of antitumor T cells into the tumor. The treatment is well tolerated and leads to robust anti-tumor response in the aggressive B16F10 model. These results suggest that NKTR-214 could improve the efficacy of ACT protocols tested in humans.
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| Overall design |
C57/BL6 mice were implanted subcutaneously with B16F10 syngeneic murine melanoma cell line. When the tumors reached the volume of at least 150mm3, mice received adoptive cell transfer of pmel-1 T cells with NKTR-214 or IL-2. Tumors from three biological replicates were harvested at day 12 after treatment .
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| Contributor(s) |
Parisi G, Saco J, Bergara F, Tsoi J, Krystofinski P, Puig-Saus C, Zhang R, Zhou J, Cheung-Lau G, Grasso CS, Hu-Lieskovan S, Wu A, Comin-Anduix B, Charych DH, Ribas A |
| Citation(s) |
32005809 |
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| Submission date |
Aug 19, 2018 |
| Last update date |
Feb 10, 2020 |
| Contact name |
Jennifer Tsoi |
| E-mail(s) |
JTsoi@mednet.ucla.edu
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| Organization name |
UCLA
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| Department |
University of California, Los Angeles
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| Lab |
Thomas Graeber
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| Street address |
570 Westwood Blvd, CNSI 4338
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| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095 |
| Country |
USA |
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| Platforms (1) |
| GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA486672 |
| SRA |
SRP158333 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE118748_NKTR_IL2_ACT_FPKM_gene_expression.txt.gz |
373.8 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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