METHODS FOR ASSESSING CELL SURFACE GLYCOSYLATION

    公开(公告)号:US20210255173A1

    公开(公告)日:2021-08-19

    申请号:US16604547

    申请日:2018-04-13

    IPC分类号: G01N33/53 C12Q1/34 G01N33/50

    摘要: Provided herein are methods for assessing cell surface glycans, e.g., N-glycans, by assessing a sample of released surface glycans, and determining the presence, absence, or level of glycans present in the sample. Also provided are methods of assaying and/or evaluating a cell composition by assessing the cell surface glycan profile of the cell composition and comparing the profile to a reference sample. Methods for manufacturing and/or culturing a plurality of cell compositions having consistent surface glycan expression with low variability are also provided.

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

    公开(公告)号:US11020429B2

    公开(公告)日:2021-06-01

    申请号:US15773153

    申请日:2016-11-04

    摘要: 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.

    Engineered cells for adoptive cell therapy

    公开(公告)号:US10786533B2

    公开(公告)日:2020-09-29

    申请号:US15744744

    申请日:2016-07-15

    摘要: Provided are engineered cells for adoptive therapy, including NK cells and T cells. Also provided are compositions for engineering and producing the cells, compositions containing the cells, and methods for their administration to subjects. In some embodiments, the cells contain genetically engineered antigen receptors that specifically bind to antigens, such as chimeric antigen receptors (CARs) and costimulatory receptors. In some embodiments, the cells include receptors targeting multiple antigens. In some embodiments, the cells include repression of one or more gene product, for example, by disruption of a gene encoding the gene product. In some embodiments, a gene encoding an antigen recognized by the engineered antigen receptor is disrupted, reducing the likelihood of targeting of the engineered cells. In some embodiments, the antigen recognized by the engineered antigen receptor is related to a tumor antigen recognized by the engineered antigen receptor.

    METHODS AND COMPOSITIONS FOR DOSING IN ADOPTIVE CELL THERAPY

    公开(公告)号:US20200054680A1

    公开(公告)日:2020-02-20

    申请号:US16667564

    申请日:2019-10-29

    发明人: Mark J. GILBERT

    摘要: Provided are methods for administering multiple doses of cells, such as T cells, to subjects for cell therapy. Also provided are compositions and articles of manufacture for use in the methods. The cells generally express recombinant receptors such as chimeric receptors, e.g., chimeric antigen receptors (CARs) or other transgenic receptors such as T cell receptors (TCRs). The methods generally involve administering a first and at least one consecutive dose of the cells. Timing of the doses relative to one another, and/or size of the doses, in some embodiments provide various advantages such as lower or reduced toxicity and improved efficacy, for example, due to increased exposure of the subject to the administered cells. In some embodiments, the first dose is a relatively low dose, such as one that reduces tumor or disease burden, thereby improving the efficacy of consecutive or subsequent doses, and the consecutive dose is a consolidating dose.

    IMMUNOTHERAPY METHODS AND COMPOSITIONS INVOLVING TRYPTOPHAN METABOLIC PATHWAY MODULATORS

    公开(公告)号:US20200054673A1

    公开(公告)日:2020-02-20

    申请号:US16340085

    申请日:2017-10-13

    摘要: Provided are methods of treatment involving immunotherapy, such as T cell therapy, and administration of a tryptophan metabolism and/or kynurenine pathway modulator. In some embodiments, the method includes a combination therapy that involves administration of engineered T cells, such as chimeric antigen receptor (CAR)-expressing cells, and a tryptophan metabolism and/or kynurenine pathway modulator, such as an inhibitor of an enzyme. Also provided are engineered cells in which the expression of a molecule involved in the kynurenine pathway is modified. Also provided are methods of manufacturing engineered cells, cells, compositions, methods of administration to subjects, nucleic acids and kits for use in the methods. In some aspects, features of the methods and cells provide for increased or improved activity, activity, outcome, function, response, persistence, expansion and/or proliferation of cells for adoptive cell therapy.