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Series GSE118748 Query DataSets for GSE118748
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
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.
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 .
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
Submission date Aug 19, 2018
Last update date Feb 10, 2020
Contact name Jennifer Tsoi
Organization name UCLA
Department University of California, Los Angeles
Lab Thomas Graeber
Street address 570 Westwood Blvd, CNSI 4338
City Los Angeles
State/province CA
ZIP/Postal code 90095
Country USA
Platforms (1)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (6)
GSM3346364 IL2-1-T12
GSM3346365 IL2-2-T12
GSM3346366 IL2-3-T12
BioProject PRJNA486672
SRA SRP158333

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Supplementary file Size Download File type/resource
GSE118748_NKTR_IL2_ACT_FPKM_gene_expression.txt.gz 373.8 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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