Bloodworks

University of Washington

Fred Hutchinson Cancer Center

Puget Sound Blood Center

Bloodworks Northwest

Junmei Chen

Jose Lopez

Dominic W Chung

Xiaoyun Fu

Jose Aron Lopez

Minhua Ling

Stanley R Riddell

Cameron J Turtle

David G Maloney

W Conrad Liles

Barbara A Konkle

Mark M Wurfel

Shelby A Cate

The instant disclosure provides biomarkers and methods for identifying subjects at risk of developing cytokine release syndrome (CRS), neurotoxicity, or both after adoptive immunotherapy to guide preemptive intervention, modified therapy, or the like. For example, adverse event biomarkers may be measured in a subject before pre-conditioning chemotherapy, before immunotherapy (e.g., adoptive immunotherapy infusion comprising a chimeric antigen receptor (CAR) modified T cell), or shortly after pre-conditioning chemotherapy and/or immunotherapy. Exemplary biomarkers include temperature, cytokine levels and endothelial activation biomarkers, such as angiopoietin 2, von Willebrand factor (vWF), ratio of angiopoietin 2 to angiopoietin 1, and ratio of ADAMTS13 to vWF. Also provided are methods of treating subjects identified as at risk of developing cytokine release syndrome (CRS), neurotoxicity, or both to minimize such potential adverse events.

Biomarkers and uses thereof for selecting immunotherapy intervention

Compositions and methods are described for preventing or reducing protein loss due to protein aggregation, denaturation, and absorption to surfaces. Also described are compositions and methods for preventing or reducing the fouling or clogging of medical devices that come into contact with blood, such as catheters. Also described are methods to treat diseases caused by activation of the microvasculature.

Protein stabilizing factors

Compositions and methods for determining the level of thiol and disulfide containing molecules in a sample are provided. The compositions and methods can be used to determine the level of oxidative stress in a subject with or without antioxidant treatment. Also provided are biomarkers of oxidative stress.

Determination of small-molecule thiols and disulfides: protein bound cys and total cysteine as biomarkers of oxidative stress

Compositions and methods are described for preventing or reducing protein loss due to protein aggregation, denaturation, and adsorption to surfaces. Also described are compositions and methods for preventing or reducing the fouling or clogging of medical devices that come into contact with blood, such as catheters. Also described are methods to treat diseases caused by activation of the microvasculature.

Novel methods are described for measuring the rate of ADAMTS13-mediated cleavage of von Willebrand Factor (VWF) multimers. Through the use of the reagent, ristocetin, the method can advantageously be performed in the absence of an applied shear stress or added denaturing agent. Also described are methods for diagnosing ADAMTS13-associated disorders and methods for providing improved treatment of those disorders by evaluating the efficacy of the treatment using the methods as described.

Determination of von Willebrand Factor cleavage by ADAMTS13

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Seattle, WA, United States of America

Junmei Chen