Abstract: Provided are methods, compositions and articles of manufacture for use in cell therapy involving the administration of one or more doses of a therapeutic T cell composition, and methods, compositions and articles of manufacture for use in the same. 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 embodiments of the present disclosure, including the dose of cells or units of cells administered and/or the phenotype of administered cells, provide various advantages, such as consistent dosing, lower risk of toxicity and/or increased response in subjects administered the T cell compositions.

Abstract: Disclosed herein are engineered AAV VP capsid polypeptides with the ability to assemble into virus particles and having improved tissue tropism to eye tissues, for example, retinal tissues, retinal pigment epithelial cells, or photoreceptor cells. The capsids are engineered using the high throughput discovery system described herein. In certain embodiments, provided herein are recombinant adeno-associated virus (AAV) VP capsid polypeptides having at least one mutation in a 581 to 589 region of the VP capsid polypeptide, corresponding to residues 581 to residue 589 of a VP1 polypeptide of SEQ ID NO: 1.

Abstract: A method of modeling enhancer activity obtains a training dataset in electronic form. The dataset comprises a plurality of training enhancers and, for each such enhancer, a corresponding measured amount of activity of the enhancer in each of one or more states. Each enhancer is a tandem repeat. A model comprising a plurality of parameters is trained by inputting each training enhancer into the model. Upon input, the model applies the parameters to the training enhancer to generate, as model output, a corresponding predicted activity of the training enhancer for a first state of the one or more states. The plurality of parameters is refined based differentials between corresponding measured and predicted amounts of activity in the first state for each of the training enhancer. A plurality of test enhancers is generated using the trained model and their activity tested thereby modeling enhancer activity.

Abstract: Systems and methods for generating a polymer sequence for a biological molecule having one or more target biological properties are provided. A plurality of target metric values for one or more target biological properties of a biological molecule and a seed for a nucleic acid or amino acid sequence for the biological molecule are inputted into a conditional generator model of a conditional generative adversarial network to obtain as output from the conditional generator model a nucleic acid or amino acid sequence for the biological molecule that is predicted by the conditional generator model to confer on the biological molecule the one or more target biological properties approximating the plurality of target metric values.

Abstract: Provided are methods, compositions and articles of manufacture for use in cell therapy involving the administration of one or more doses of a therapeutic T cell composition, and methods, compositions and articles of manufacture for use in the same. 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 embodiments of the present disclosure, including the dose of cells or units of cells administered and/or the phenotype of administered cells, provide various advantages, such as consistent dosing, lower risk of toxicity and/or increased response in subjects administered the T cell compositions.

Abstract: 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.

Abstract: 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.

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 are methods for determining or predicting attributes of therapeutic cell compositions in connection with 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 correlations between input composition (e.g., starting material derived from subjects for producing a cell therapy) attributes and therapeutic cell composition attributes.

Abstract: Provided herein is a model, in particular a mouse model, for assessing or evaluating toxicity to an immunotherapy, for example a therapeutic cell therapy, such as a cell therapy containing engineered cells, such as T cells, expressing a recombinant receptor, e.g. a chimeric antigen receptor (CAR). Also provided is a method for generating the mouse model. Also provided herein are methods of use for the mouse models of toxicity, such as to evaluate modified or alternative immunotherapies, and/or to evaluate test agents, including agents to assess as potential interventions to reduce, prevent, or ameliorate toxicity to immunotherapy in human subjects and/or for use in combination with an immunotherapy, e.g. CAR?T cell therapy.

Abstract: Provided are methods, compositions and articles of manufacture for use in cell therapy involving the administration of one or more doses of a therapeutic T cell composition, and methods, compositions and articles of manufacture for use in the same. 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 embodiments of the present disclosure, including the dose of cells or units of cells administered and/or the phenotype of administered cells, provide various advantages, such as consistent dosing, lower risk of toxicity and/or increased response in subjects administered the T cell compositions.

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: The present disclosure relates in some aspects to methods, compositions and uses involving immunotherapies, such as adoptive cell therapy, e.g., T cell therapy, and an immunomodulatory compound, such as a structural or functional analog or derivative of thalidomide and/or an inhibitor of E3-ubiquitin ligase. The provided methods, compositions and uses include those for combination therapies involving the administration or use of one or more immunomodulatory compounds in conjunction with a T cell therapy, such as a genetically engineered T cell therapy involving cells engineered with a recombinant receptor, such as chimeric antigen receptor (CAR)-expressing T cells. Also provided are compositions, methods of administration to subjects, articles of manufacture and kits for use in the methods.

Abstract: 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.