Abstract: The present invention provides for the intratumoral delivery of immunomodulators. hi particular, it provides delivery of co-stimulatory molecules using intratumoral electroporation. The present invention provides a method for the treatment of malignancies, wherein the administration of a plasmid encoding for a therapeutic costimulatory protein, in combination with electroporation has a therapeutic effect on primmy tumors as well as distant tumors and metastases.

Abstract: Provided are plasmid vector constructs encoding multiple immunomodulatory proteins where each protein or component thereof can be expressed utilizing appropriate promotors and/or translation modifiers. Additional immunomodulatory proteins and genetic adjuvants containing shared tumor antigens can be added to further therapeutic potential as well as allow tracking of therapeutic treatment. Also provides are methods of expressing the plasmid constructs.

Abstract: The present invention provides for the intratumoral delivery of at least one immunostimulatory cytokine in combination with at least one checkpoint inhibitor. In particular, it provides delivery of a plasmid encoding the immunostimulatory cytokine using intratumoral electroporation. The checkpoint inhibitor may be administered systemically or encoded on a plasmid and delivered using intratumoral electroporation. The checkpoint inhibitor may be delivered contemporaneously with or after treatment with the immunomodulatory cytokine.

Abstract: An adaptive control method for controlling EP pulse parameters during electroporation (EP) of cells or tissue using an EP system includes providing a system for adaptive control to optimize EP pulse parameters including EP pulse parameters, applying voltage and current excitation signals to the cells, obtaining data from the current and voltage measurements, and processing the data to separate the desirable data from the undesirable data, extracting relevant features from the desirable data, applying at least a portion of the relevant features to a trained diagnostic model, estimating EP pulsing parameters based on an outcome of the applied relevant features, where the initialized EP pulsing parameters are based on the trained model and the relevant features, to optimize the EP pulsing parameters, and applying, by the generator, a first EP pulse based on the first pulsing parameters.

Abstract: An adaptive control method for controlling EP pulse parameters during electroporation (EP) of cells or tissue using an EP system includes providing a system for adaptive control to optimize EP pulse parameters including EP pulse parameters, applying voltage and current excitation signals to the cells, obtaining data from the current and voltage measurements, and processing the data to separate the desirable data from the undesirable data, extracting relevant features from the desirable data, applying at least a portion of the relevant features to a trained diagnostic model, estimating EP pulsing parameters based on an outcome of the applied relevant features, where the initialized EP pulsing parameters are based on the trained model and the relevant features, to optimize the EP pulsing parameters, and applying, by the generator, a first EP pulse based on the first pulsing parameters.

Abstract: The present disclosure provides processes for describing and quantifying the expression of human programmed death ligand-1 (PD-L1) in tumor tissue sections as detected by immunohistochemical assay using an antibody that specifically binds to PD-L1. The results generated using these processes have a variety of experimental, diagnostic and prognostic applications.

Abstract: The present invention provides for a dosing schedule for the intratumoral delivery of an immunostimulatory cytokine in combination with systemic delivery of a checkpoint inhibitor. In particular, it provides delivery of a plasmid encoding the immunostimulatory cytokine, e.g., IL-12, using intratumoral electroporation, and the systemic delivery of a PD-1 antagonist.

Abstract: The present invention relates, in part, to certain cancer biomarkers and use thereof in methods for treating cancer, such as in evaluating and/or predicting patient responses to treatment with a CXCR4 inhibitor optionally in combination with a immunotherapeutic agent, in patients with a cancer such as melanoma, including resectable and unresectable melanoma. The present invention also provides a biomarker expression platform, which is a combination of a set of genes or biomarkers that are correlated with response to a CXCR4 inhibitor in a tumor as well as a normalization gene set. A method and system of using the biomarker expression platform to derive biomarker signatures of anti-tumor response and to test patient samples for predictive biomarker signatures are also disclosed.

Abstract: The present invention provides for a dosing schedule for the intratumoral delivery of an immunostimulatory cytokine in combination with systemic delivery of a checkpoint inhibitor. In particular, it provides delivery of a plasmid encoding the immunostimulatory cytokine, e.g., IL-12, using intratumoral electroporation, and the systemic delivery of a PD-1 antagonist.

Abstract: Provided are plasmid vector constructs encoding multiple immunomodulatory proteins where each protein or component thereof can be expressed utilizing appropriate promoters and/or translation modifiers. Additional immunomodulatory proteins and genetic adjuvants containing shared tumor antigens can be added to further therapeutic potential as well as allow tracking of therapeutic treatment. Also provides are methods of expressing the plasmid constructs.

Abstract: The present invention provides for the intratumoral delivery of at least one immunostimulatory cytokine in combination with at least one checkpoint inhibitor. In particular, it provides delivery of a plasmid encoding the immunostimulatory cytokine using intratumoral electroporation. The checkpoint inhibitor may be administered systemically or encoded on a plasmid and delivered using intratumoral electroporation. The checkpoint inhibitor may be delivered contemporaneously with or after treatment with the immunomodulatory cytokine.

Abstract: The present invention provides for the intratumoral delivery of at least one immunostimulatory cytokine in combination with at least one checkpoint inhibitor. In particular, it provides delivery of a plasmid encoding the immunostimulatory cytokine using intratumoral electroporation. The checkpoint inhibitor may be administered systemically or encoded on a plasmid and delivered using intratumoral electroporation. The checkpoint inhibitor may be delivered contemporaneously with or after treatment with the immunomodulatory cytokine.

Abstract: The present disclosure describes an IHC assay for detecting and quantifying spatially proximal pairs of PD-1-expressing cells (PD-1+ cells) and PD-Ligand-expressing cells (PD-L+ cells) in tumor tissue, and the use of the assay to generate proximity biomarkers that are predictive of which cancer patients are most likely to benefit from treatment with a PD-1 antagonist. The disclosure also provides methods for testing tumor samples for the proximity biomarkers, as well as methods for treating subjects with a PD-1 antagonist based on the test results.

Abstract: The present invention provides for a dosing schedule for the intratumoral delivery of an immunostimulatory cytokine in combination with systemic delivery of a checkpoint inhibitor. In particular, it provides delivery of a plasmid encoding the immunostimulatory cytokine, e.g., IL-12, using intratumoral electroporation, and the systemic delivery of a PD-1 antagonist.

Abstract: Provided are plasmid vector constructs encoding multiple immunomodulatory proteins where each protein or component thereof can be expressed utilizing appropriate promotors and/or translation modifiers. Additional immunomodulatory proteins and genetic adjuvants containing shared tumor antigens can be added to further therapeutic potential as well as allow tracking of therapeutic treatment. Also provides are methods of expressing the plasmid constructs.

Abstract: An adaptive control method for controlling EP pulse parameters during electroporation (EP) of cells or tissue using an EP system includes providing a system for adaptive control to optimize EP pulse parameters including EP pulse parameters, applying voltage and current excitation signals to the cells, obtaining data from the current and voltage measurements, and processing the data to separate the desirable data from the undesirable data, extracting relevant features from the desirable data, applying at least a portion of the relevant features to a trained diagnostic model, estimating EP pulsing parameters based on an outcome of the applied relevant features, where the initialized EP pulsing parameters are based on the trained model and the relevant features, to optimize the EP pulsing parameters, and applying, by the generator, a first EP pulse based on the first pulsing parameters.

Abstract: The present disclosure describes an IHC assay for detecting and quantifying spatially proximal pairs of PD-1-expressing cells (PD-1+ cells) and PD-Ligand-expressing cells (PD-L+ cells) in tumor tissue, and the use of the assay to generate proximity biomarkers that are predictive of which cancer patients are most likely to benefit from treatment with a PD-1 antagonist. The disclosure also provides methods for testing tumor samples for the proximity biomarkers, as well as methods for treating subjects with a PD-1 antagonist based on the test results.

Abstract: The present invention provides for the intratumoral delivery of at least one immunostimulatory cytokine in combination with at least one checkpoint inhibitor. In particular, it provides delivery of a plasmid encoding the immunostimulatory cytokine using intratumoral electroporation. The checkpoint inhibitor may be administered systemically or encoded on a plasmid and delivered using intratumoral electroporation. The checkpoint inhibitor may be delivered contemporaneously with or after treatment with the immunomodulatory cytokine.

Abstract: The present disclosure provides processes for describing and quantifying the expression of human programmed death ligand-1 (PD-L1) in tumor tissue sections as detected by immunohistochemical assay using an antibody that specifically binds to PD-L1. The results generated using these processes have a variety of experimental, diagnostic and prognostic applications.

Abstract: The present invention provides for the intratumoral delivery of immunomodulators. In particular, it provides delivery of co-stimulatory molecules using intratumoral electroporation. The present invention provides a method for the treatment of malignancies, wherein the administration of a plasmid encoding for a therapeutic costimulatory protein, in combination with electroporation has a therapeutic effect on primary tumors as well as distant tumors and metastases.