Juno Therapeutics Gmbh

Fate Therapeutics, Inc.

Celgene Corporation

Lucas James Thompson

Ellen Filvaroff

Daniel D Shoemaker

Deborah Mortensen

Mark L Bonyhadi

Robert F DuBose

Betsy Rezner

David Robbins

Eigen Peralta

Jonathan Rosen

Ian Hardy

Ryan P Larson

Christian Maine

Timothy G Johnstone

Ronald James Hause, Jr

David G Kugler

Archana Brahmandam

Robert F Dubose

Provided are chimeric receptors for engineering cells for adoptive therapy, including T cells, and the genetically engineered cells. In some embodiments, the chimeric receptors, such as chimeric antigen receptors (CARs) are modified in a junction region by one or more amino acid modifications such that peptide fragments of such region exhibit a lower binding affinity for a human leukocyte antigen (HLA) and/or the region exhibits reduced immunogenicity, including following administration to a subject. In some aspects, also provided are methods and compositions for engineering and producing cells expressing such chimeric receptors, compositions containing the cells, and method for their administration to subjects. In some embodiments, features of the chimeric receptors and engineered cells containing the chimeric receptors result in methods that provide for increased or improved activity, efficacy and/or persistence.

Modified chimeric receptors and related compositions and methods

Compounds that either produce a higher proportion or greater absolute number of phenotypically identified naive, stem cell memory, central memory T cells, adaptive NK cells, and type I NKT cells are identified. Compositions and methods for modulating immune cells including T, NK, and NKT cells for adoptive cell therapies, such as those providing improvements in one or more therapeutic outcomes, are provided.

Compositions and methods for immune cell modulation in adoptive immunotherapies

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

Provided are cells, e.g., engineered immune cells, expressing recombinant or engineered molecules involved in metabolic pathways, such as those that promote or inhibit one or more metabolic steps, reactions, or pathways, for example, in T cells. Such molecules include those that induce or repress a particular functional outcome or metabolic event, for example, one that promotes differentiation or reprogramming into a particular phenotypic state, such as memory, long-lived, activated or activatable, non-exhausted, phenotype or stem-like phenotype. The cells generally further express an immune receptor, such as an antigen receptor, which may be an engineered receptor, such as a CAR or recombinant TCR, or may be a natural immune receptor. Also provided are cells, such as T cells, expressing such molecules and combinations thereof, compositions comprising such cells, nucleic acids such as vectors encoding the same, and methods of administration to subjects in adoptive cell therapy.

Vectors and genetically engineered immune cells expressing metabolic pathway modulators and uses in adoptive cell therapy

Growing community of inventors

Seattle, WA, United States of America

Lucas James Thompson