Abstract: Provided herein are methods and compositions for editing the genome of a human T cell. In some embodiments, a heterologous T cell receptor (TCR)-? chain and a heterologous TCR-? chain are inserted into exon 1 of a TCR subunit constant gene in the genome of the T cell.

Abstract: Provided herein are methods and compositions for editing the genome of a human T cell. In some embodiments, a heterologous T cell receptor (TCR)-? chain and a heterologous TCR-? chain are inserted into exon 1 of a TCR subunit constant gene in the genome of the T cell.

Abstract: Methods and compositions are provided related to therapeutic receptors, including chimeric antigen receptors (CARs), capable of specifically binding TYRP-1. The disclosed compositions include, for example, cells (e.g., immune cells) expressing TYRP-1 specific CARs, nucleic acids encoding TYRP-1 specific CARs, and TYRP-1 specific CAR polypeptides. Certain aspects relate to methods of treating cancer, including melanoma, using compositions comprising TYRP-1 specific CARs, for example cells expressing TYRP-1 specific CARs. In some embodiments, provided herein are chimeric polypeptides comprising a TYRP-1 binding domain, a hinge region, a transmembrane domain, and an intracellular signaling domain.

Abstract: Provided herein are methods and compositions for editing the genome of a human T cell. In some embodiments, a heterologous T cell receptor (TCR)-? chain and a heterologous TCR-? chain are inserted into exon 1 of a TCR subunit constant gene in the genome of the T cell.

Abstract: Provided herein are methods and compositions for editing the genome of a human T cell. In some embodiments, a heterologous T cell receptor (TCR)-? chain and a heterologous TCR-? chain are inserted into exon 1 of a TCR subunit constant gene in the genome of the T cell.

Abstract: Systems and methods for digital pathology in accordance with embodiments of the invention obtain a whole slide image of a microscope slide that includes a registration mark, wherein the registration mark is associated with a coordinate system. The method inputs the whole slide image into a region identification (RI) model to extract features of the whole slide image and generate feature vectors for the extracted features, detects a presence of a region of interest (ROI) based on the feature vectors, determines a set of coordinates of the ROI in the coordinate system, and translates a microscope stage of a microscope holding the microscope slide to a position corresponding to the coordinates of the ROI. The method captures a field of view (FOV) image with the microscope and inputs the FOV image into a grading model to determine a pathology score that indicates a likelihood of a presence of a disease.

Abstract: Provided are methods and compositions directed towards the treatment of an individual having cancer by providing adoptive cell transfer therapy and administering to the individual a long-acting IL-2R?-biased agonist.

Abstract: A method of analyzing a biological sample from a subject that has a tumor or cancer, comprising: determining, for target cells having a phenotype of interest spatial resolution of the target cells, density of the spatially resolved target cells in the sample; and proximity between spatially resolved target cells of interest in the sample; and determining an overall score based at least in part on the preceding parameters. A method for identifying a patient as a responder to single agent anti-PD-1 or anti-PD-L1 therapy is provided. Similar methods are provided for detecting adaptive immune resistance, the presence of cancer in a patient sample, determining efficacy of cancer therapy, and determining response to and monitoring the efficacy of cancer therapy.

Abstract: Disclosed herein are improved methods of treating cancer in a subject by administering Adoptive Cell Therapy, in particular in those subjects affected by a cancer that presents a loss of function, mutation, or other disruption in an immune pathway. The loss of function mutation or disruption can be in IFNAR1, JAK2, or B2M. The methods include the intratumoral administration of nanoplexed poly(TC) formulations. These methods are further useful for a variety of therapeutic methods and uses relating to the administration of an immune checkpoint therapy such as anti-PD 1 or anti-PDL1 for the prevention of, and/or against the occurrence of cancer, particularly solid cancer.

Abstract: Provided herein are methods and compositions for editing the genome of a human T cell. In some embodiments, a heterologous T cell receptor (TCR)-? chain and a heterologous TCR-? chain are inserted into exon 1 of a TCR subunit constant gene in the genome of the T cell.

Abstract: Tumor-specific T cell receptor (TCR) gene transfer enables specific and potent immune targeting of tumor antigens. The canonical cancer-testis antigen, NY-ESO-1, is not expressed in normal tissues but is aberrantly expressed across a broad array of cancer types. It has also been targeted with A2-restricted TCR gene therapy without adverse events or notable side effects. To enable the targeting of NY-ESO-1 in a broader array of HLA haplotypes, we isolated TCRs specific for NY-ESO-1 epitopes presented by four MHC molecules: HLA-A2, -B07, -B18, and -C03. Using these TCRs, we have developed an approach to extend TCR gene therapies targeting NY-ESO-1 to patient populations beyond those expressing HLA-A2.

Abstract: Provided herein are methods and compositions for editing the genome of a human T cell. In some embodiments, a heterologous T cell receptor (TCR)-? chain and a heterologous TCR-? chain are inserted into exon 1 of a TCR subunit constant gene in the genome of the T cell.

Abstract: Provided herein are methods and compositions for editing the genome of a human T cell. In some embodiments, a heterologous T cell receptor (TCR)-? chain and a heterologous TCR-? chain are inserted into exon 1 of a TCR subunit constant gene in the genome of the T cell.

Abstract: Provided herein are methods and compositions for editing the genome of a human T cell. In some embodiments, a heterologous T cell receptor (TCR)-? chain and a heterologous TCR-? chain are inserted into exon 1 of a TCR subunit constant gene in the genome of the T cell.

Abstract: Disclosed herein are methods of treating cancer in a subject, comprising: administering at least one PAK4 inhibitor to the subject; and in certain embodiments administering at least one immunostimulatory agent to the subject. In some aspects, the immunostimulatory agent can be a checkpoint inhibitor. In certain aspects the checkpoint inhibitor can be an anti-PD1 antibody.

Abstract: Methods of predicting or detecting sensitivity to therapeutic effects of anti-PD-1 therapy in a patient suffering from melanoma, as well as for selecting somatic mutanomes and transcriptomes of melanoma biopsies. A tumor sample obtained from the patient is assayed for a measure of anti-PD-1 therapy sensitivity via, for example, whole transcriptome sequencing, antibody based protein quantifications, mass spectrometry based protein quantification, targeted mRNA sequencing, real-time RT-PCR, Sanger sequencing, targeted sequencing and/or whole exome/genome sequencing. Samples are selected that exhibit a higher first enrichment similarity score and/or a lower second enrichment similarity score, and/or at least one measure of sensitivity. A patient whose sample was selected herein as a candidate for anti-PD-1 therapy is thereby identified. The method of the invention can further comprise treating the patient with anti-PD-1 therapy, optionally in conjunction with combinatorial therapy.

Abstract: Disclosed herein are methods of treating or assessing cancer in a subject wherein it has been determined whether the cancer comprises a loss of function mutation or disruption in an immune pathway. The loss of function mutation or disruption can be in JAK1 or JAK2. The loss of function mutation or disruption can be in B2M. The methods can include administering an immune checkpoint therapy such as anti-PD1 or anti-PDL1. The methods can include administering an alternative therapy to an immune checkpoint therapy. In some aspects, the method includes determining whether the cancer comprises a loss of function mutation or disruption in an immune pathway.

Abstract: The current methods and compositions provide for a novel therapeutic method for treating patients diagnosed with melanoma, especially those that have become resistant to certain other therapies. Accordingly, certain aspects of the disclosure relate to a method for treating melanoma in a subject, the method comprising administering a composition comprising a ferroptosis-inducing agent or other dedifferentiated melanoma-targeting agent to the subject.

Abstract: Provided are methods and compositions directed towards the treatment of an individual having cancer by providing adoptive cell transfer therapy and administering to the individual a long acting IL-2R??-biased agonist.

Abstract: Provided herein are methods and compositions for editing the genome of a human T cell. In some embodiments, a heterologous T cell receptor (TCR)-? chain and a heterologous TCR-? chain are inserted into exon 1 of a TCR subunit constant gene in the genome of the T cell.