Fred Hutchinson Cancer Center

Seattle Children's Hospital

University of Washington

Juno Therapeutics Gmbh

Fred Hutchinson Cancer Research Center

The United States of America, as Represented by the Secretary, Department of Health and Human Services

City of Hope

Bloodworks Northwest

City of Home

Seattle Children's Hospital Dba Seattle Children's Research Institute

Stanley R Riddell

Michael Hudecek

Michael C Jensen

Cameron J Turtle

Lingfeng Liu

Susanna Carolina Berger

Philip D Greenberg

Damian J Green

Joshua Veatch

Ashwini Balakrishnan

Julie Randolph-Habecker

Benjamin G Hoffstrom

David G Maloney

Christoph Rader

Mark J Gilbert

Colin Correnti

He Li

Jose Lopez

Junmei Chen

Dominic W Chung

Melissa Works

Colleen Delaney

W Conrad Liles

Mark M Wurfel

Tyler Hill

Carla A Jaeger

Sylvia Lee

Shivani Srivastava

David Maloney

Carolina Berger

The present disclosure provides binding proteins, such as TCRs, that specifically bind various tumor associated antigens (including human BRAFV600E epitope), cells expressing such antigen specific binding proteins, nucleic acids encoding the same, and compositions for use in treating diseases or disorders in which cells express BRAFV600E, such as in cancer.

BRAF-specific TCRs and uses thereof

Engineered trimeric CD70 proteins for use in ex vivo T cell manufacturing are described. Use of the proteins during manufacturing creates expanded T cell populations with enhanced properties such as earlier proliferation in culture; selective expansion of nave and memory T cell subsets; longer persistence in vivo following administration to a subject; and improved therapeutic effect. Use of the proteins as therapeutics provide anti-cancer and anti-viral effects. The proteins can also be used as agonistic cell culture reagents in in vitro uses.

Engineered trimeric CD70 proteins and uses thereof

The present disclosure provides reagents and methods for treating disease using modified immune cells (e.g., T cell comprising CAR or TCR) in combination with an agent associated with induction of immunogenic cell death (ICD) and optionally further in combination with an agent that specifically binds to and/or inhibits an immune suppression component and/or an agonist of an immune stimulatory molecule.

Methods for improving adoptive cell therapy

Provided herein are combination therapies involving administration of an immunotherapy involving a cell therapy, such as a T cell therapy, and an inhibitor of gamma secretase. Also provided are methods for engineering, preparing, and producing the cells, compositions containing the cells and/or gamma secretase inhibitor, and kits and devices containing and for using, producing and administering the cells and/or gamma secretase inhibitor, such as in accord with the provided combination therapy methods.

Combination of a cell therapy and a gamma secretase inhibitor

The present disclosure relates to tagged chimeric effector molecules and receptor molecules thereof for genetically engineering a host cell, wherein the recombinant host cell can be identified, isolated, sorted, induced to proliferate, tracked or eliminated. For example, a T cell may be recombinantly modified for use in adoptive immunotherapy.

Tagged chimeric effector molecules and receptors thereof

The present disclosure relates to anti-ROR1 binding proteins, including those that bind to a ROR1 or portion thereof such as an intracellular C terminal portion of a ROR1 protein, and the use of such binding proteins in immunohistochemical and diagnostic methods. Related kits and methods of using the binding proteins are also provided, as are methods of treatment of subjects having diseases or conditions determined to be candidates for such treatments by the binding proteins or methods of this disclosure.

Anti-ROR1 antibodies and uses thereof

The present disclosure relates to methods for using BCMA-specific binding molecules (such as a BCMA-specific chimeric antigen receptor or antibody) in combination with γ-secretase inhibitors, which can be done concurrently or sequentially, to treat or prevent a B-cell related proliferative disease, such as a cancer or autoimmune disease, or the like. A BCMA-specific binding molecule in combination with γ-secretase inhibitor can be used in, for example, adoptive immunotherapy.

Combination therapies for treatment of BCMA-related cancers and autoimmune disorders

Stem cells are modified to express an extracellular component including a tag cassette. The tag cassette can be used to detect, enrich, isolate, activate, track, deplete, or eliminate modified cells. The cells can be administered before or following differentiation into a more committed cell type.

Modified stem cells and uses thereof

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 present disclosure relates to immune cells that express an exogenous neoantigen and an immunogenicity enhancer, or to T cells that express an exogenous neoantigen, and their use in treating a disease or disorder, such as cancer for tumor associated neoantigens. Related expression constructs, kits, host cells, pharmaceutical compositions, and methods are also provided.

Cell-based neoantigen vaccines and uses thereof

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

The present invention provides methods and compositions to confer and/or augment immune responses mediated by cellular immunotherapy, such as by adoptively transferring genetically modified tumor specific CD8+ T cells in the presence of tumor-specific, subset specific genetically modified CD4+ T cells, wherein the CD4+ T cells confer and/or augment a CD8+ T cells ability to sustain anti-tumor reactivity and increase and/or maximize tumor-specific proliferation of the tumor-specific CD8+ T cells of interest. Pharmaceutical formulations produced by the method, and methods of using the same, are also described.

Method and compositions for cellular immunotherapy

The present invention provides a method of carrying out adoptive immunotherapy in a primate subject in need thereof by administering the subject a cytotoxic T lymphocytes (CTL) preparation in a treatment-effective amount. The method comprises administering as the CTL preparation a preparation consisting essentially of an in vitro expanded primate CTL population, the CTL population enriched prior to expansion for central memory T lymphocytes, and depleted prior to expansion of effector memory T lymphocytes. In some embodiments, the method may further comprise concurrently administering Interleukin-15 to the subject in an amount effective to increase the proliferation of the central memory T cells in the subject. Pharmaceutical formulations produced by the method, and methods of using the same, are also described.

Adoptive transfer of CD8+ T cell clones derived from central memory cells

Growing community of inventors

Sammamish, WA, United States of America

Stanley R Riddell