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: 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: 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: 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: The instant disclosure provides biomarkers and methods for identifying subjects at risk of relapse or suitable for allogeneic hematopoietic stem cell transplant after adoptive immunotherapy to guide preemptive intervention, modified therapy, or the like. Exemplary biomarkers include pre-lymphodepletion levels of serum lactate dehydrogenase (LDH), pre-lymphodepletion levels of platelets, levels of MCP-1, levels of IL-17, and pre-treatment regimen disease pathology. Based on the determined risk-relapse profile, an at-risk subject may be treated with pre-emptive therapy, while a subject not at risk for relapse may not receive further treatment, or may receive an allogeneic hematopoietic stem cell transplant. Also provided are methods for treating a hematological malignancy, wherein certain embodiments of the methods comprise adoptive cell therapy in the context of BTK-inhibitor therapy and/or BTK-inhibitor therapy in the context of adoptive cell therapy.

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: Provided are adoptive cell therapy methods involving the administration of doses of cells for treating B cell malignancies. The cells generally express recombinant receptors such as chimeric antigen receptors (CARs). In some embodiments, the methods are for treating subjects with chronic lymphocytic leukemia (CLL). In some embodiments, the methods are for treating subjects with non-Hodgkin lymphoma (NHL). In some embodiments, the methods involve prior administration of a lymphodepleting therapy, such as prior administration of fluradibine and/or another lymphodepleting chemotherapeutic agent, for example cyclophosphamide. In some embodiments, features of the methods include an increase in complete remission, overall survival and/or progression free survival of subjects treated in accord with the provided methods.

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: 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: 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.