Profound inhibition of antigen-specific T-cell effector functions by dasatinib

Ralf Weichsel; Carolin Dix; Linda Wooldridge; Matthew Clement; Angharad Fenton-May; Andrew K Sewell; Josef Zezula; Elisabeth Greiner; Emma Gostick; David A Price; Hermann Einsele; Ruth Seggewiss

doi:10.1158/1078-0432.CCR-07-4393

Profound inhibition of antigen-specific T-cell effector functions by dasatinib

Ralf Weichsel, Carolin Dix, Linda Wooldridge, Matthew Clement, Angharad Fenton-May, Andrew K Sewell, Josef Zezula, Elisabeth Greiner, Emma Gostick, David A Price, Hermann Einsele, Ruth Seggewiss

Research output: Contribution to journal › Article (Academic Journal) › peer-review

126 Citations (Scopus)

Abstract

The dual BCR-ABL/SRC kinase inhibitor dasatinib entered the clinic for the treatment of chronic myeloid leukemia and Ph+ acute lymphoblastic leukemia. Because SRC kinases are known to play an important role in physiologic T-cell activation, we analyzed the immunobiological effects of dasatinib on T-cell function. The effect of dasatinib on multiple T-cell effector functions was examined at clinically relevant doses (1-100 nmol/L); the promiscuous tyrosine kinase inhibitor staurosporine was used as a comparator.

Original language	English
Pages (from-to)	2484-91
Number of pages	8
Journal	Clinical Cancer Research
Volume	14
Issue number	8
DOIs	https://doi.org/10.1158/1078-0432.CCR-07-4393
Publication status	Published - 15 Apr 2008

Keywords

Apoptosis
Cells, Cultured
Dose-Response Relationship, Drug
Humans
Immunologic Memory
Interleukin-2
Lymphocyte Activation
Protein Kinase Inhibitors
Pyrimidines
Receptor-CD3 Complex, Antigen, T-Cell
Receptors, Antigen, T-Cell
Staurosporine
T-Lymphocytes
Thiazoles

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title = "Profound inhibition of antigen-specific T-cell effector functions by dasatinib",

abstract = "The dual BCR-ABL/SRC kinase inhibitor dasatinib entered the clinic for the treatment of chronic myeloid leukemia and Ph+ acute lymphoblastic leukemia. Because SRC kinases are known to play an important role in physiologic T-cell activation, we analyzed the immunobiological effects of dasatinib on T-cell function. The effect of dasatinib on multiple T-cell effector functions was examined at clinically relevant doses (1-100 nmol/L); the promiscuous tyrosine kinase inhibitor staurosporine was used as a comparator.",

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author = "Ralf Weichsel and Carolin Dix and Linda Wooldridge and Matthew Clement and Angharad Fenton-May and Sewell, {Andrew K} and Josef Zezula and Elisabeth Greiner and Emma Gostick and Price, {David A} and Hermann Einsele and Ruth Seggewiss",

year = "2008",

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doi = "10.1158/1078-0432.CCR-07-4393",

language = "English",

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T1 - Profound inhibition of antigen-specific T-cell effector functions by dasatinib

AU - Weichsel, Ralf

AU - Dix, Carolin

AU - Wooldridge, Linda

AU - Clement, Matthew

AU - Fenton-May, Angharad

AU - Sewell, Andrew K

AU - Zezula, Josef

AU - Greiner, Elisabeth

AU - Gostick, Emma

AU - Price, David A

AU - Einsele, Hermann

AU - Seggewiss, Ruth

PY - 2008/4/15

Y1 - 2008/4/15

N2 - The dual BCR-ABL/SRC kinase inhibitor dasatinib entered the clinic for the treatment of chronic myeloid leukemia and Ph+ acute lymphoblastic leukemia. Because SRC kinases are known to play an important role in physiologic T-cell activation, we analyzed the immunobiological effects of dasatinib on T-cell function. The effect of dasatinib on multiple T-cell effector functions was examined at clinically relevant doses (1-100 nmol/L); the promiscuous tyrosine kinase inhibitor staurosporine was used as a comparator.

AB - The dual BCR-ABL/SRC kinase inhibitor dasatinib entered the clinic for the treatment of chronic myeloid leukemia and Ph+ acute lymphoblastic leukemia. Because SRC kinases are known to play an important role in physiologic T-cell activation, we analyzed the immunobiological effects of dasatinib on T-cell function. The effect of dasatinib on multiple T-cell effector functions was examined at clinically relevant doses (1-100 nmol/L); the promiscuous tyrosine kinase inhibitor staurosporine was used as a comparator.

KW - Apoptosis

KW - Cells, Cultured

KW - Dose-Response Relationship, Drug

KW - Humans

KW - Immunologic Memory

KW - Interleukin-2

KW - Lymphocyte Activation

KW - Protein Kinase Inhibitors

KW - Pyrimidines

KW - Receptor-CD3 Complex, Antigen, T-Cell

KW - Receptors, Antigen, T-Cell

KW - Staurosporine

KW - T-Lymphocytes

KW - Thiazoles

U2 - 10.1158/1078-0432.CCR-07-4393

DO - 10.1158/1078-0432.CCR-07-4393

M3 - Article (Academic Journal)

C2 - 18413841

SN - 1078-0432

VL - 14

SP - 2484

EP - 2491

JO - Clinical Cancer Research

JF - Clinical Cancer Research

IS - 8

ER -

Profound inhibition of antigen-specific T-cell effector functions by dasatinib

Abstract

Keywords

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