Juno Therapeutics Gmbh

Life Technologies Corporation

Xcyte Therapies, Inc.

Invitrogen Corporation

Mark L Bonyhadi

Dale Kalamasz

Ronald Jay Berenson

Che Law

Alan Hardwick

David McMillen

Stewart Craig

Pascal Beauchesne

Narinder Saund

Chris Ramsborg

Calvin Chan

Ryan P Larson

Harjinder Singh Chana

David Mcmillen

Christopher Glen Ramsborg

Clinton Weber

Nathan K Yee

Lucas James Thompson

Ryan L Crisman

Timothy G Johnstone

Ronald James Hause, Jr

Mary Mallaney

David G Kugler

Zahbea Saund

Sarah Y Lee

John Matthew Wesner

Alan R Hardwick

The present disclosure relates in some aspects to methods, cells, and compositions for preparing cells and compositions for genetic engineering and cell therapy. Provided in some embodiments are streamlined cell preparation methods, e.g., for isolation, processing, incubation, and genetic engineering of cells and populations of cells. Also provided are cells and compositions produced by the methods and methods of their use. The cells can include immune cells, such as T cells, and generally include a plurality of isolated T cell populations or types. In some aspects, the methods are capable of preparing of a plurality of different cell populations for adoptive therapy using fewer steps and/or resources and/or reduced handling compared with other methods.

Methods for isolating, culturing, and genetically engineering immune cell populations for adoptive therapy

The present disclosure provides methods for genetically engineering T cells, such as CD4+ T cells, for use in cell therapy. In some aspects, the provided methods include one or more steps for incubating the cells under stimulating conditions, introducing a recombinant polypeptide to the cells through transduction or transfection, and cultivating the cells under conditions that promote proliferation and/or expansion. In some aspects, the incubation and/or the cultivation is performed in the presence of recombinant IL-2. In some aspects, the provided methods are an efficient, reliable means to produce genetically engineered T cells with a high degree of success.

Process for generating therapeutic compositions of engineered cells

Provided herein are methods of identifying genomic region(s) predictive of an outcome of treatment with a cell therapy and/or of a phenotype of function of the cells. In some embodiments, the methods include epigenetic and/or epigenomic analyses of the cells in connection with methods for preparing engineered cells for cell therapy and/or predicting response to a cell therapy, e.g., engineered cells for cell therapy. In some embodiments, the methods include steps to assess, characterize and analyze changes or modifications in an epigenetic property of gene region or regions, such as chromatin accessibility, nucleosome occupancy, histone modification, spatial chromosomal conformation, transcription factor occupancy and/or DNA methylation. In some embodiments, the epigenetic and/or epigenomic analysis includes determining the epigenetic properties of a cell, e.g., an engineered cell for cell therapy.

Epigenetic analysis of cell therapy and related methods

The present invention relates generally to methods for stimulating T cells, and more particularly, to methods to eliminate undesired (e.g., autoreactive, alloreactive, pathogenic) subpopulations of T cells from a mixed population of T cells, thereby restoring the normal immune repertoire of said T cells. The present invention also relates to compositions of cells, including stimulated T cells having restored immune repertoire and uses thereof.

Methods for eliminating at least a substantial portion of a clonal antigen-specific memory T cell subpopulation

The present invention relates generally to methods for generating, expanding, and isolating antigen-specific T cells. Compositions of antigen-specific T cells activated and expanded by the methods herein are further provided.

Generation and isolation of antigen-specific T cells

The present invention relates generally to methods for activating and expanding cells, and more particularly, to a novel method to activate and/or stimulate cells that maximizes the expansion of such cells to achieve dramatically high densities. In the various embodiments, cells are activated and expanded to very high densities in a short period of time. In certain embodiments, cells are activated and expanded to very high numbers of cells in a short period of time. Compositions of cells activated and expanded by the methods herein are further provided.

Activation and expansion of T cells

Activation and expansion of cells

The present invention relates generally to methods for stimulating cells, and more particularly, to a novel method to concentrate and stimulate cells that maximizes stimulation and/or proliferation of such cells. In the various embodiments, cells are stimulated and concentrated with a surface yielding enhanced proliferation, cell signal transduction, and/or cell surface moiety aggregation. In certain aspects methods for stimulating a population of cells such as T-cells, by simultaneous concentration and cell surface moiety ligation are provided by contacting the population of cells with a surface, that has attached thereto one or more agents that ligate a cell surface moiety and applying a force that predominantly drives cell concentration and cell surface moiety ligation, thereby inducing cell stimulation, cell surface moiety aggregation, and/or receptor signaling enhancement. Also provided are methods for producing phenotypically tailored cells, including T-cells for the use in diagnostics, drug discovery, and the treatment of a variety of indications, including cancer, viral infection, and immune related disorders. Compositions of cells having specific phenotypic properties produced by these processes are further provided.

Simultaneous stimulation and concentration of cells

The present invention relates generally to methods for stimulating cells, and more particularly, to a novel method to concentrate and/or stimulate cells that maximizes stimulation and/or proliferation of such cells. In the various embodiments, cells are stimulated and concentrated with a surface yielding enhanced proliferation, cell signal transduction, and/or cell surface moiety aggregation. In certain aspects methods for stimulating a population of cells such as T-cells, by simultaneous concentration and cell surface moiety ligation are provided by contacting the population of cells with a surface, that has attached thereto one or more agents that ligate a cell surface moiety and applying a force that predominantly drives cell concentration and cell surface moiety ligation, thereby inducing cell stimulation, cell surface moiety aggregation, and/or receptor signaling enhancement. Also provided are methods for producing phenotypically tailored cells, including T-cells for the use in diagnostics, drug discovery, and the treatment of a variety of indications, including cancer, viral infection, and immune related disorders. Compositions of cells having specific phenotypic properties produced by these processes are further provided.

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Sammamish, WA, United States of America

Mark L Bonyhadi