Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 137, Issue 9, Pages 3229-3232Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jacs.5b00620
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- National Institutes of Health [2 R01 GM097206-05]
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM097206] Funding Source: NIH RePORTER
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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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