Fred Hutchinson Cancer Center

University of Washington

Juno Therapeutics Gmbh

Bloodworks Northwest

Fred Hutchinson Cancer Research Center

Cameron J Turtle

Stanley R Riddell

David G Maloney

Mark J Gilbert

He Li

Junmei Chen

Jose Lopez

Dominic W Chung

W Conrad Liles

Mark M Wurfel

David Maloney

Provided are methods, kits and compositions related to toxicity associated with administration of cell therapy for the treatment of diseases or conditions, e.g., cancer, including methods for use in predicting and treating a toxicity. In some embodiments, the toxicity is a neurotoxicity or cytokine release syndrome (CRS), such as a severe neurotoxicity or a severe CRS. The methods generally involve detecting a parameter of a biomarker or individually a parameter of each biomarker in a panel of biomarkers, such as a concentration, amount or activity, and comparing the detected parameter to a reference value for the parameter to determine if the subject is at risk for developing the toxicity, such as neurotoxicity or CRS or severe neurotoxicity or severe CRS. In some embodiments, the methods further involve administering an agent or therapy for treating, ameliorating, preventing, delaying and/or attenuating the development of the toxicity, such as neurotoxicity or CRS, such as severe neurotoxicity or severe CRS.

Methods and compositions related to toxicity associated with cell therapy

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

This invention provides, among other things, methods for the identification and isolation of viable putative long-lived antigen-specific memory CD8T cell subsets (CMhi and EMhi) with high surface expression of CD161 and/or IL-18R&#x3b1; and the capacity to rapidly efflux the fluorescent dye Rh123.

Identification of CD8T cells that are CD161and/or IL18R(&#x3b1;)and have rapid drug efflux capacity

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Seattle, WA, United States of America

Cameron J Turtle