Abstract: 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.

Abstract: Combination therapies that include (i) an immune cell that expresses a chimeric antigen receptor (CAR) or similar molecule and (ii) a compound that preserves or potentiates the in vivo actions of tumor necrosis factor alpha (TNF?) against cancer cells are described. The combination therapies result in the killing of antigen-negative cells in the vicinity of immunotherapy targeted-antigen-positive cells reducing the survivability of escape variants and providing other benefits.

Abstract: Chimeric antigen receptors (CARs) with binding domains derived from a novel suite of human CD33-binding antibodies are described. The CARs include optimized short and intermediate spacer regions. The current disclosure also provides methods of cell expansion/activation processes utilizing IL-2, IL-7, IL-15, and/or IL-21 that improve cellular proliferation and cell lysis of the CARs as described.

Abstract: Provided are methods and compositions directed to the treatment of an individual having cancer by (i) administering to the individual an adoptive cellular immunotherapy composition comprising CAR T cells and (ii) administering to the individual an interleukin-15 receptor agonist, such as, for example, a long-acting interleukin-15 receptor agonist.

Abstract: Chimeric antigen receptors (CARs) with binding domains derived from a novel suite of CD33-binding antibodies are described. The CARs include optimized short and intermediate spacer regions. The current disclosure also provides methods of cell expansion/activation processes utilizing IL-2, IL-7, IL-15, and/or IL-21 that improve cellular proliferation and cell lysis of the CARs as described.

Abstract: 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.

Abstract: This invention provides, among other things, methods for the identification and isolation of viable putative long-lived antigen-specific memory CD8+ T cell subsets (CMhi and EMhi) with high surface expression of CD161 and/or IL-18R? and the capacity to rapidly efflux the fluorescent dye Rh123.

Abstract: This invention provides, among other things, methods for the identification and isolation of viable putative long-lived antigen-specific memory CD8+ T cell subsets (CMhi and EMhi) with high surface expression of CD161 and/or IL-18R? and the capacity to rapidly efflux the fluorescent dye Rh123.

Abstract: This invention provides, among other things, methods for the identification and isolation of viable putative long-lived antigen-specific memory CD8+ T cell subsets (CMhi and EMhi) with high surface expression of CD161 and/or IL-18R? and the capacity to rapidly efflux the fluorescent dye Rh123.

Abstract: This invention provides, among other things, methods for the identification and isolation of viable putative long-lived antigen-specific memory CD8+ T cell subsets (CMhi and EMhi) with high surface expression of CD161 and/or IL-18R? and the capacity to rapidly efflux the fluorescent dye Rh123.

Abstract: This invention provides, among other things, methods for the identification and isolation of viable putative long-lived antigen-specific memory CD8+ T cell subsets (CMhi and EMhi) with high surface expression of CD161 and/or IL-18R? and the capacity to rapidly efflux the fluorescent dye Rh123.

Abstract: This invention provides, among other things, methods for the identification and isolation of viable putative long-lived antigen-specific memory CD8+ T cell subsets (CMhi and EMhi) with high surface expression of CD161 and/or IL-18R? and the capacity to rapidly efflux the fluorescent dye Rh123.