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J Am Chem Soc. 2015 Mar 11;137(9):3229-32. doi: 10.1021/jacs.5b00620. Epub 2015 Feb 27.

An immunosuppressive antibody-drug conjugate.

Author information

1
Department of Chemistry and the Skaggs Institute for Chemical Biology and ‡Department of Immunology and Microbial Science, The Scripps Research Institute , La Jolla, California 92037, United States.

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.

PMID:
25699419
PMCID:
PMC4472444
DOI:
10.1021/jacs.5b00620
[Indexed for MEDLINE]
Free PMC Article

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