An immunosuppressive antibody-drug conjugate

Rongsheng E. Wang; Tao Liu; Ying Wang; Yu Cao; Jintang Du; Xiaozhou Luo; Vishal Deshmukh; Chan Hyuk Kim; Brian R. Lawson; Matthew S. Tremblay; Travis S. Young; Stephanie A. Kazane; Feng Wang; Peter G. Schultz

doi:10.1021/jacs.5b00620

An immunosuppressive antibody-drug conjugate

Rongsheng E. Wang, Tao Liu, Ying Wang, Yu Cao, Jintang Du, Xiaozhou Luo, Vishal Deshmukh, Chan Hyuk Kim, Brian R. Lawson, Matthew S. Tremblay, Travis S. Young, Stephanie A. Kazane, Feng Wang, Peter G. Schultz

Research output: Contribution to journal › Article › peer-review

92 Scopus citations

Abstract

We have developed a novel antibody-drug conjugate (ADC) that can selectively deliver the Lck inhibitor dasatinib to human T lymphocytes. This ADC is based on a humanized antibody that selectively binds with high affinity to CXCR4, an antigen that is selectively expressed on hematopoietic cells. The resulting dasatinib-antibody conjugate suppresses T-cell-receptor (TCR)-mediated T-cell activation and cytokine expression with low nM EC₅₀ and has minimal effects on cell viability. This ADC may lead to a new class of selective immunosuppressive drugs with improved safety and extend the ADC strategy to the targeted delivery of kinase inhibitors for indications beyond oncology.

Original language	English
Pages (from-to)	3229-3232
Number of pages	4
Journal	Journal of the American Chemical Society
Volume	137
Issue number	9
DOIs	https://doi.org/10.1021/jacs.5b00620
State	Published - Feb 2015
Externally published	Yes

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title = "An immunosuppressive antibody-drug conjugate",

abstract = "We have developed a novel antibody-drug conjugate (ADC) that can selectively deliver the Lck inhibitor dasatinib to human T lymphocytes. This ADC is based on a humanized antibody that selectively binds with high affinity to CXCR4, an antigen that is selectively expressed on hematopoietic cells. The resulting dasatinib-antibody conjugate suppresses T-cell-receptor (TCR)-mediated T-cell activation and cytokine expression with low nM EC50 and has minimal effects on cell viability. This ADC may lead to a new class of selective immunosuppressive drugs with improved safety and extend the ADC strategy to the targeted delivery of kinase inhibitors for indications beyond oncology.",

author = "Wang, {Rongsheng E.} and Tao Liu and Ying Wang and Yu Cao and Jintang Du and Xiaozhou Luo and Vishal Deshmukh and Kim, {Chan Hyuk} and Lawson, {Brian R.} and Tremblay, {Matthew S.} and Young, {Travis S.} and Kazane, {Stephanie A.} and Feng Wang and Schultz, {Peter G.}",

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doi = "10.1021/jacs.5b00620",

language = "English",

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TY - JOUR

T1 - An immunosuppressive antibody-drug conjugate

AU - Wang, Rongsheng E.

AU - Liu, Tao

AU - Wang, Ying

AU - Cao, Yu

AU - Du, Jintang

AU - Luo, Xiaozhou

AU - Deshmukh, Vishal

AU - Kim, Chan Hyuk

AU - Lawson, Brian R.

AU - Tremblay, Matthew S.

AU - Young, Travis S.

AU - Kazane, Stephanie A.

AU - Wang, Feng

AU - Schultz, Peter G.

PY - 2015/2

Y1 - 2015/2

N2 - We have developed a novel antibody-drug conjugate (ADC) that can selectively deliver the Lck inhibitor dasatinib to human T lymphocytes. This ADC is based on a humanized antibody that selectively binds with high affinity to CXCR4, an antigen that is selectively expressed on hematopoietic cells. The resulting dasatinib-antibody conjugate suppresses T-cell-receptor (TCR)-mediated T-cell activation and cytokine expression with low nM EC50 and has minimal effects on cell viability. This ADC may lead to a new class of selective immunosuppressive drugs with improved safety and extend the ADC strategy to the targeted delivery of kinase inhibitors for indications beyond oncology.

AB - We have developed a novel antibody-drug conjugate (ADC) that can selectively deliver the Lck inhibitor dasatinib to human T lymphocytes. This ADC is based on a humanized antibody that selectively binds with high affinity to CXCR4, an antigen that is selectively expressed on hematopoietic cells. The resulting dasatinib-antibody conjugate suppresses T-cell-receptor (TCR)-mediated T-cell activation and cytokine expression with low nM EC50 and has minimal effects on cell viability. This ADC may lead to a new class of selective immunosuppressive drugs with improved safety and extend the ADC strategy to the targeted delivery of kinase inhibitors for indications beyond oncology.

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U2 - 10.1021/jacs.5b00620

DO - 10.1021/jacs.5b00620

M3 - Article

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SN - 0002-7863

VL - 137

SP - 3229

EP - 3232

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 9

ER -

An immunosuppressive antibody-drug conjugate

Abstract

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