Abstract: Systems and methods are presented that allow for selection of tumor neoepitopes that are then used to generate a recombinant polytope that is optimized for proper trafficking and processing. In preferred methods, the polytope is encoded in a viral expression system that is used as a therapeutic agent.

Abstract: Cancer immunotherapy is enhanced by co-expression of cancer associated or tumor-specific (neo)epitopes with co-stimulatory molecules and/or other immune activators. Where desired, treatment may be enhanced by administration of a immune checkpoint inhibitor.

Abstract: In certain embodiments, methods and compositions are provided for generating immune responses against tumor neo-antigens or neo-epitopes. In particular embodiments there may be provided methods for constructing and producing recombinant adenovirus-based vector vaccines containing nucleic acid sequences encoding tumor neo-antigens and neo-epitopes that allow for vaccinations in individuals with preexisting immunity to adenovirus. In additional embodiments, methods and compositions are provided for the treatment of cancer using immunotherapy based on recombinant adenovirus-based vectors combined with engineered natural killer cells. In some embodiments, the methods and compositions further comprises a nucleic acid encoding for an immunological fusion partner.

Abstract: Contemplated panomic systems and methods significantly improve accuracy of genetic testing by taking into account matched normal data and expression levels of various genes in diseased tissue. Analysis and physician guidance is further improved by combining so identified clinically relevant changes with pathway analysis to thereby allow for classification of a tumor and/or identification of potentially druggable targets within affected pathways.

Abstract: Methods of isolating cell free RNA from individual's bodily fluid and reliably obtain cell free RNA data are presented, preferably by use of high-stability portions and/or use of targeted small amplicons on the cell free RNA.

Abstract: Techniques are provided for predicting DNA accessibility. DNase-seq data files and RNA-seq data files for a plurality of cell types are paired by assigning DNase-seq data files to RNA-seq data files that are at least within a same biotype. A neural network is configured to be trained using batches of the paired data files, where configuring the neural network comprises configuring convolutional layers to process a first input comprising DNA sequence data from a paired data file to generate a convolved output, and fully connected layers following the convolutional layers to concatenate the convolved output with a second input comprising gene expression levels derived from RNA-seq data from the paired data file and process the concatenation to generate a DNA accessibility prediction output. The trained neural network is used to predict DNA accessibility in a genomic sample input comprising RNA-seq data and whole genome sequencing for a new cell type.

Abstract: Various compounds, compositions, and methods for inhibition of Rit1 are presented. In especially preferred aspects, contemplated compounds and compositions are suitable for treatment of cancers and other diseases associated with Rit1 signaling.

Abstract: Compositions and methods for isolation and use of cfRNA are disclosed. Most preferably the cfRNA includes a patient-and tumor-specific mutation, and/or encodes a gene that is relevant in immune response or immune suppression. The identity and/or quantity of cfRNA can be further used for diagnosis of tumor, monitoring of prognosis of the tumor, monitoring the effectiveness of treatment provided to the patients, evaluating a treatment regime based on a likelihood of success of the treatment regime, and even as discovery tool that allows repeated and non-invasive sampling of a patient.

Abstract: Systems and methods are contemplated that use various omics data for DNA repair genes to assess a health associated parameter for an individual.

Abstract: Contemplated compositions and methods use various immunomodulatory agents to downregulate an autoimmune response and/or to upregulate immune responses against autoantigen presenting cells.

Abstract: Omics patient data are analyzed using sequences or diff objects of tumor and matched normal tissue to identify patient and disease specific mutations, using transcriptomic data to identify expression levels of the mutated genes, and pathway analysis based on the so obtained omic data to identify specific pathway characteristics for the diseased tissue. Most notably, many different tumors have shared pathway characteristics, and identification of a pathway characteristic of a tumor may thus indicate effective treatment options ordinarily not considered when tumor analysis is based on anatomical tumor type only.

Abstract: RNA from a biological fluid is stabilized during isolation and/or storage using DNA. In especially preferred aspects, the RNA is cfRNA and/or ctRNA, and the biological fluid is blood.

Abstract: Cancer is treated using coordinated treatment regimens that uses various compounds and compositions that drive a tumor from the escape phase of cancer immunoediting to the elimination and equilibrium phase of cancer immunoediting.

Abstract: The invention relates to a method of modeling K-Ras proteins with one or more mutations that result in constitutive activity, and identifying compounds that inhibit interactions among activated K-Ras proteins and their upstream and downstream effectors.

Abstract: Systems and methods for validating immune therapy that targets patient- and tumor-specific neoepitopes are presented in which cellular components are identified and/or used that present patient- and tumor-specific neoepitopes. Presence of these neoepitopes confirms the suitability of the neoepitopes. Advantageously, synthetic antibodies are created based on in silico analysis of the tumor genome and RNA or phage display, and can be used to isolate cellular components, and especially circulating tumor cells, metastatic cells, and/or exosomes and microvesicles.

Abstract: Circulating free RNA (cfRNA) and/or circulating tumor RNA (ctRNA) are employed to identify and quantitate expression levels of various genes and further allows for non-invasive monitoring of changes in such genes. Moreover, analysis of ct/cfRNA (and ct/cfDNA) enable detection, prediction, and monitoring of cancer status based on the presence of circulating free cfRNA and/or ctRNA, and further identify or determine a treatment and the response to the treatment.

Abstract: Cancer immunotherapy using genetically engineered NK cells is enhanced by expression of recombinant co-stimulatory molecules to deliver co-stimulatory signals to a recipient host's immune cells to enhance an immune response.

Abstract: Omics patient data are analyzed using sequences or diff objects of tumor and matched normal tissue to identify patient and disease specific mutations, using transcriptomic data to identify expression levels of the mutated genes, and pathway analysis based on the so obtained omic data to identify specific pathway characteristics for the diseased tissue. Most notably, many different tumors have shared pathway characteristics, and identification of a pathway characteristic of a tumor may thus indicate effective treatment options ordinarily not considered when tumor analysis is based on anatomical tumor type only.

Abstract: cfRNA is used to identify and quantitate expression levels of disease related genes and further allows for non-invasive monitoring of changes in such genes. Moreover, quantitative analysis of disease related genes will enable prediction of treatment response where the treatment is dependent on the presence of the disease related gene.

Abstract: Methods for targeting a tumor antigen for immunotherapy based on HLA allele type and the mutations present in the tumor antigen are presented. A patient's HLA allele type and a tumor antigen derived from a mutation in cancer driver gene can be matched with a majority allele type having a minimum affinity to the same tumor antigen or with those of a plurality of patients with a history of cancer treatment. Upon matching, a cancer treatment against the tumor antigen can be selected and administered to the patient to achieve a desired effect.