Abstract: Provided are combination therapies involving immunotherapies e.g., a chimeric antigen receptor (CAR) T cell therapy, and the use of a kinase inhibitor, e.g., a BTK/1TK inhibitor, e.g. Ibrutinib, for treating subjects having cancers, such as certain B cell malignancies, and related methods, compositions, uses and articles of manufacture. The CART cell therapy includes cells that express recombinant receptors such as anti-CD19 CARS. In some embodiments, the B-cell malignancy is a non-Hodgkin lymphoma (NHL), such as relapsed or refractory NHL or specific NHL subtype.

Abstract: Provided herein are methods for determining if a subject is at risk for developing a toxicity, e.g., neurotoxicity, following administration of a therapy, such as an immunotherapy or cell therapy, e.g., a chimeric antigen receptor (CAR) T cell therapy based on the expression, in a sample obtained from the subject, of one or more genes or gene products that are associated with and/or correlate to a risk of developing toxicity following administration of the therapy. In some aspects, the sample is a sample obtained from the subject prior to receiving the therapy. Also provided are methods for treating a subject having a disease or condition, such as acute lymphoblastic leukemia (ALL), according to a particular treatment regimen, in some cases involving administration of the immunotherapy or cell therapy, based on assessment of risk of developing a toxicity following administration of the therapy. Also provided herein are reagents and kits for performing the methods.

Abstract: Provided are CCT5-binding molecules, including anti-CCT5 antibodies and antigen- binding fragments thereof such as heavy chain variable (VH) regions and single-chain antibody fragments, and conjugates comprising the anti-CCT5 binding molecules such as immunoconjugates and antibody-drug conjugates, and chimeric receptors comprising the anti-CCT5 binding molecules such as chimeric antigen receptors (CARs). In some embodiments, the anti-CCT5 antibodies or antigen-binding fragments thereof specifically bind to CCT5. Also provided are genetically engineered cells expressing the CARs or CCT5-binding molecules and uses thereof such as in adoptive cell therapy.

Abstract: Provided herein are methods for engineering immune cells, cell compositions containing engineered immune cells, kits and articles of manufacture for targeting nucleic acid sequence encoding a portion of a recombinant receptor, e.g., a recombinant T cell receptor (TCR), to a particular genomic locus and/or for modulating expression of the gene at the genomic locus, and applications thereof in connection with cancer immunotherapy, such as adoptive transfer of engineered T cells. In some aspects, the nucleic acid sequence integrates in-frame into the locus of a receptor encoding gene, and in some aspects, results in expression of the whole recombinant receptor.

Abstract: Provided are methods for engineering immune cells, cell compositions containing engineered immune cells, kits and articles of manufacture for targeting nucleic acid sequence encoding a recombinant receptor to a particular genomic locus and/or for modulating expression of the gene at the genomic locus, and applications thereof in connection with cancer immunotherapy comprising adoptive transfer of engineered T cells. These may involve genetic disruption of at least one site within a TRAC gene and/or a TRBC gene and integration of the transgene encoding for the recombinant receptor at or near one of the at least one target site.

Abstract: Provided are ROR1 binding molecules, including anti-ROR1 antibodies, including antibody fragments such as variable heavy chain (VH) regions, single-chain fragments, and chimeric receptors including the antibodies, such as chimeric antigen receptors (CARs). In some embodiments, the antibodies specifically bind to ROR1. Among the antibodies are human antibodies, including those that compete for binding to ROR1 with reference antibodies, such as a non-human reference antibody. Also provided are genetically engineered cells expressing the chimeric receptors, and uses of the binding molecules and cells adoptive cell therapy.

Abstract: Provided herein are BCMA-binding molecules, including anti-BCMA antibodies and antigen-binding fragments thereof such as heavy chain variable (VH) regions and single-chain antibody fragments, and chimeric receptors comprising the anti-BCMA binding molecules such as chimeric antigen receptors (CARs). In some embodiments, the anti-BCMA antibodies or antigen-binding fragments thereof specifically bind to BCMA-1. Among the anti-BCMA antibodies are human antibodies, including those that compete for binding to BCMA with reference antibodies, such as a non-human reference antibody. Also provided are genetically engineered cells expressing the CARs or BCMA-binding molecules and uses thereof such as in adoptive cell therapy.

Abstract: Provided are methods of detecting, assessing or determining the presence or absence of particles, such as bead particles, present in a cell composition. Also provided are articles of manufacture and kits for use in the methods.

Abstract: 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.

Abstract: The present disclosure provides methods for genetically engineering T cells, such as CD4+ T cells and/or CD8+ T cells, for use in cell therapy. In some aspects, the provided methods include one or more steps for pooling enriched CD4+ and CD8+ cells, such as at a 1:1 ratio, and then incubating the cells under stimulating conditions, introducing a recombinant polypeptide to the cells through transduction or transfection, and/or cultivating the cells under conditions that promote proliferation and/or expansion. In some aspects, the provided methods are an efficient, reliable means to produce genetically engineered T cells with a high degree of success.

Abstract: 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.

Abstract: The present disclosure is directed to closed-system cryogenic vessels for biomedical material with needleless removal. The needleless removal can reduce damage to biomedical material inside the vessel, allow for greater recovery of biomedical material from the vessel, and reduce exposure risk to users of the closed-system cryogenic vessels during removal of the biomedical material from the vessel. In some aspects, the vessels can be used to store or package a composition of cells, such as a composition containing engineered cells, including in connection with adoptive cell therapy. Also provided are articles of manufacture, kits and methods.

Abstract: 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 aspects, features of the cells and methods provide specificity and/or efficacy. 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.

Abstract: 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.

Abstract: Provided are methods of administering peptides containing portions of or corresponding to an agent to be administered, such as a cell or molecule expressed by such cell such as a recombinant protein such as a chimeric receptor. In some embodiments, the administration is in conjunction with treatment methods employing the agent, e.g., cell or chimeric receptor, such as adoptive cell therapy methods. The chimeric receptor can be a chimeric antigen receptor (CAR). The peptides contain an epitope of the recombinant receptor and, in some embodiments, are capable of downregulating or reducing immune responses against the chimeric receptor, such as CAR. Also provided are such peptides and compositions that can induce tolerance to an agent such as a chimeric receptor, such as a CAR.

Abstract: Provided herein are methods for tracking certain cells associated with a cell therapy, such as from a starting cell composition or a sample prior to administration to a subject and from a sample following administration to a subject. In some aspects, the methods include assessing one or more parameters or attributes of such cells and methods of identifying cellular attributes associated with particular desired cells. The provided methods can be used in connection with cell therapy including adoptive transfer of engineered T cells or T cell precursors.

Abstract: 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.

Abstract: 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 aspects, features of the cells and methods provide specificity and/or efficacy. 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.

Abstract: Provided are methods for preparing T cells for cell therapy, compositions produced by the methods, and methods of administering the cells to subjects. In particular, the disclosure relates to preparation of engineered T cells, such as those expressing genetically engineered receptors, such as genetically engineered antigen receptors such as engineered (recombinant) TCRs and chimeric antigen receptors (CARs), or other recombinant chimeric receptors. Features of the methods include producing a more consistent and/or predictable T cell product and/or lower toxicity compared with other methods. The provided methods include incubating cells under stimulating conditions to induce expansion or proliferation of naive-like T cells compared to non-naive like T cells in the stimulated composition, which in turn can result in preferential transduction of cells derived from the naive-like T cells.

Abstract: Provided herein are methods, compositions and articles of manufacture for use in connection with cell therapy involving the administration of one or more doses of a therapeutic T cell composition. The cells of the T cell composition express recombinant receptors such as chimeric receptors, e.g. chimeric antigen receptors (CARs) or other transgenic receptors such as T cell receptors (TCRs). Features of the provided embodiments, including the numbers of cells or units of cells administered and/or the potency of administered cells, provide various advantages, such as lower risk of toxicity in subjects administered the T cell compositions.