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Series GSE102617 Query DataSets for GSE102617
Status Public on Feb 01, 2018
Title CART-19 Responses in Human CD19 Transgenic Mice [immunology platform]
Organism Mus musculus domesticus
Experiment type Expression profiling by array
Summary The clinical success of chimeric antigen receptor (CAR) T-cell therapy for CD19+ B-cell malignancies may come at the expense of acute and chronic morbidities. Some patients suffer from significant, acute toxicities and those with persistent CAR T-cells require immunoglobulin therapy due to CAR-induced B-cell aplasia. Life-threatening effects include cytokine release syndrome, the exact etiology of which is unclear. To elucidate the underlying mechanisms of CAR-induced toxicities, we developed a mouse model in which human CD19 (hCD19)-specific mouse CAR T-cells were adoptively transferred into mice whose normal B-cells express a hCD19 transgene at hemizygous levels. In contrast to homozygous mice, hemizygous mice have higher B cell frequencies, providing a greater target antigen load to drive CAR-T cell activation. Hemizygous mice given a lethal dose of hCD19 transgene-expressing lymphoma cells and treated with CAR-T cells had undetectable levels of tumor. However, recipients experienced acute B-cell aplasia, morbidities and mortality in an antigen- and dose-dependent manner. IL-6, INF-g, and inflammatory pathway transcripts were enriched in affected tissues. As in patients, antibody-mediated neutralization of IL-6 blunted toxicity. This new model will prove useful in testing strategies designed to improve CD19-specific CAR T-cell therapy by reducing acute toxicities and reversing B-cell aplasia.
 
Overall design mRNA was extracted from colons and spleens from human CD19 transgenic mice 2 and 5 days after adoptive transfer of 3E+06 human CD19-specific CAR T-cells (or control hEGFRT-cells). mRNA for 561 unique genes were quantitated on the nanoString mouse immunology codeset. 48 samples/codeset= 40 unique samples (8 groups x 5 biological replicates/group) + 8 technical replicates (1 for each of 8 samples).
 
Contributor(s) Pennell CA, Barnum JL, McDonald-Hyman CS, Panoskaltsis-Mortari A, Riddle MJ, Xiong Z, Loschi M, Thangavelu G, Campbell HM, Refaeli Y, Furlan SN, Jensen MC, Kean LS, Miller JS, Tolar J, Osborn MJ, Blazar BR
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NIH grant(s)
Grant ID Grant title Affiliation Name
R01 CA072669 Cytotoxic-T-Lymphocyte (CTL) Therapy of AML UNIVERSITY OF MINNESOTA Bruce R. Blazar
P01 CA065493 Optimizing CAR T Cell Therapy UNIVERSITY OF MINNESOTA Bruce R. Blazar
Submission date Aug 14, 2017
Last update date Feb 01, 2018
Contact name Christopher A Pennell
E-mail(s) penne001@umn.edu
Phone 612-625-7138
Organization name University of Minnesota
Department Laboratory Medicine & Pathology
Street address 420 Delaware St SE
City Minneapolis
State/province Minnesota
ZIP/Postal code 55455
Country USA
 
Platforms (1)
GPL23907 UMN MCC nCounter Mouse 561 Immunology genes
Samples (48)
GSM2741805 CART-19_Day2_Mouse#6_Colon [1 2 6C_rep1]
GSM2741806 CART-19_Day2_Mouse#6_Colon [1 2 6C_rep2]
GSM2741807 CART-19_Day2_Mouse#7_Colon [2 2 7C_rep1]
This SubSeries is part of SuperSeries:
GSE102621 CART-19 Responses in Human CD19 Transgenic Mice
Relations
BioProject PRJNA398230

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE102617_non_normalized_immunology.txt.gz 46.3 Kb (ftp)(http) TXT
Processed data included within Sample table
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