Abstract: Provided are methods and articles of manufacture for use with cell therapy for the treatment of diseases or conditions, e.g., cancer, including for 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 marker by assaying a biological sample from a subject that is a candidate for treatment, optionally with a cell therapy, 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 and articles of manufacture further includes a regent for assaying the biological sample and instructions for determining the percentage or number of cells positive for the marker in the biological sample.

Abstract: Provided herein are binding molecules, such as those that recognize or bind a peptide epitope of a cancer antigen, such as expressed on a cancer cell, including cells infected with human papilloma virus (HPV) or that contain HPV DNA sequences and/or those that recognize or bind a peptide epitope of HPV 16 E6 or E7, in the context of a major histocompatibility complex (MHC) molecule. Among the provided binding molecules are T cell receptors (TCRs) or antibodies, including antigen-binding fragments thereof, that bind or recognize such peptide epitopes. The present disclosure further relates to engineered cells comprising such binding molecules, e.g., TCRs or antibodies (and chimeric antigen receptors containing the antibodies), and uses thereof in adoptive cell therapy.

Abstract: The present disclosure provides compositions and methods for stimulating, enriching, expanding, and/or activating engineered cells that express a recombinant receptor, e.g., a chimeric antigen receptor. In some embodiments, the provided methods include ex vivo or in vitro stimulation, enrichment, expansion, and/or activation of cells by incubation with a particle, e.g., a bead particle, attached to a binding molecule, such as a polypeptide antigen or anti-idiotype antibody, that recognizes or binds to the recombinant receptor. Also provided herein are methods for transfecting or transducing cells that have not been previously incubated with an activating or stimulating agent, such as have not been incubated with anti-CD3/anti-CD28 antibodies and/or one or more recombinant cytokines, by transducing or transfecting the cells in the presence of the particles with attached binding molecules. In some embodiments, the provided compositions can be used in methods to prepare cells, e.g.

Abstract: Provided are methods of detecting replication competent virus, e.g., replication competent retrovirus such as gammaretrovirus or lentivirus, in a sample containing a cell transduced with a viral vector particle encoding a recombinant and/or heterologous molecule, e.g., heterologous gene product. The methods may include assessing transcription of one or more target genes, such as viral genes, that are expressed in a retrovirus but not expressed in the viral vector particle. Replication competent retrovirus may be determined to be present if the levels of RNA of the one or more target genes is higher than a reference value, which can be measured directly or indirectly, including from a positive control sample containing RNA from the respective target gene at a known level and/or at or above the limit of detection of the assay.

Abstract: Provided in some aspects are compositions of cells for treating subjects with disease and conditions such as non-Hodgkin's lymphoma (NHL), and related methods, compositions, uses and articles of manufacture. In some embodiments, the disease or condition is a B-cell non-Hodgkin lymphoma (B-cell NHL). The cells generally express recombinant receptors such as chimeric antigen receptors (CARs) for targeting an antigen, such as CD 19, on cells of the lymphoma.

Abstract: Provided are anti-idiotype antibodies that specifically recognize anti-GPRC5D antibody moieties, in particular, anti-GPRC5D antibody moieties present in recombinant receptors, including chimeric antigen receptors (CARs). The disclosure further relates to uses of antiidiotype antibodies for specifically identifying and/or selecting cells expressing such recombinant receptors, such as anti-GPRC5D CAR T cells. The disclosure further relates to uses of anti-idiotype antibodies for specifically activating such cells.

Abstract: 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.

Abstract: Provided are cells, such as engineered cells, that express a prostate-specific membrane antigen (PSMA) or a modified form thereof. In some embodiments, the cell further contains a genetically engineered recombinant receptor, such as a chimeric antigen receptor, that specifically binds to an antigen. The present disclosure also provides methods of detecting, identifying, selecting or targeting cells expressing PSMA, such as in connection with administration of such cells to subjects, including methods of adoptive cell therapy, or in connection with methods of manufacturing engineered cells.

Abstract: Provided herein are methods of producing engineered T cell compositions enriched for CD57 negative and/or CD27 positive T cells, such as from a plurality of donors. In some embodiments, the T cells are engineered with a recombinant receptor, such as a chimeric antigen receptor (CAR). Also provided herein are engineered T cell compositions containing T cells enriched for CD57 negative and/or CD27 positive T cells derived from a plurality of different donors, including compositions in which the T cells are engineered with or express a recombinant receptor (e.g. CAR). Also provided are methods of using the engineered T cell compositions in adoptive therapy, including in connection for cancer immunotherapy, such as for allogeneic therapies or for administration to one or more subjects in which the T cells are not derived from the subject(s) to whom the compositions are administered.

Abstract: Disclosed are methods and systems for producing polymer-DNA nanoparticles of a predetermined size. In one example, a method includes mixing together a first solution comprising deoxyribonucleic acid (DNA) with a second solution comprising a cationic polymer to obtain a polyplex solution, and at a predetermined time subsequent to mixing together the first solution and the second solution, adding a polyplex stabilizing agent to stabilize the size of the polyplex. In this way, transfection efficacy of the polymer-DNA nanoparticles may be improved, in particular with reference to transfection of suspension cells for production of viral vectors.

Abstract: Provided herein are methods and articles of manufacture for use with cell therapy for the treatment of diseases or conditions, e.g., cancer, including for predicting and treating a toxicity. In some embodiments, the toxicity is related to cytokine release syndrome (CRS). The methods generally involve assessing a change in a factor indicative of tumor burden in a subject that is associated with and/or correlate to a risk of developing toxicity. In some aspects, the methods can be used to determine if the subject is at risk or likely at risk for developing a toxicity following administration of the cell therapy. Also provided are methods for treating a subject having a disease or condition, in some cases involving administration of the 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: The present disclosure relates to methods for identifying features, such as attributes of subjects, therapeutic cell compositions, and input compositions used to produce therapeutic cell compositions, associated with clinical responses of subjects, e.g., patients, following treatment with the therapeutic cell composition in connection with a cell therapy. The cells of the therapeutic 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). The methods provide for the identification of features associated with clinical responses. In some embodiments, the methods can be used to determine (e.g., predict) a subject's response to treatment with the therapeutic cell composition.

Abstract: Provided herein are methods, compositions and uses for treating subjects with diseases and conditions, such as those involving or associated with B cell maturation antigen (BCMA), involving administration of a T cell therapy, such as a BCMA-targeted T cell therapy, e.g. anti-BCMA CART cells, in combination with (S)-3-[4-(4-morpholin-4-ylmethyl-benzyloxy)-1-oxo-1,3-dihydro-isoindol-2-yl]-piperidine-2, 6-dione, or a pharmaceutically acceptable salt, solvate, hydrate, stereoisomer, tautomer or racemic mixtures thereof, and compositions thereof, or in combination with (S)-4-(4-(4-(((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)methyl)benzyl)piperazin-1-yl)-3-fluorobenzonitrile, or a pharmaceutically acceptable salt, solvate, hydrate, stereoisomer, tautomer or racemic mixtures thereof, and compositions thereof. The T cell therapy includes cells that express recombinant receptors such as chimeric antigen receptors (CARs) directed against BCMA.

Abstract: Provided are adoptive cell therapy methods involving the administration of doses of cells for treating disease and conditions, including certain B cell malignancies. The cells generally express recombinant receptors such as chimeric antigen receptors (CARs). In some embodiments, the methods are for treating subjects with non-Hodgkin lymphoma (NHL). In some embodiments, the methods are for treating subjects with relapsed or refractory NHL. Also provided are articles of manufacture and prophylactic treatments in connection with adoptive therapy methods.

Abstract: Provided are methods and uses related to adoptive cell therapy involving the administration of doses of cells, such as T cells, for treating disease and conditions, including certain plasma cell malignancies. The cells express recombinant receptors such as chimeric antigen receptors (CARs) specific to B-cell maturation antigen (BCMA). In some embodiments, the methods are for treating subjects with multiple myeloma (MM).

Abstract: Provided herein are methods of 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 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.

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 in some aspects are compositions of cells for treating subjects with disease and conditions such as multiple myeloma (MM), and related methods, compositions, uses and articles of manufacture. In some embodiments, the disease or condition is a relapsed or refractory multiple myeloma (r/r MM). The cells generally express recombinant receptors such as chimeric antigen receptors (CARs) for targeting an antigen, such as BCMA, on cells of the myeloma.

Abstract: Provided herein are methods for transduction of T cells. In some embodiments, the provided methods include transduction of T cells by incubation with a retroviral vector particle, e.g., lentiviral vector, in which the cells have been selected for CCR7+ expression. The provided methods improve the process for genetically engineering T cells by increasing transduction frequency and/or by reducing the variability in transduction frequency among biological samples. Also provided are resulting cells transduced with a recombinant or heterologous gene, and compositions thereof.