Abstract: The present disclosure provides compounds of the formula (I) wherein these compounds contain a ligand which binds to one or more target proteins such as CDK4 or CDK6 and a ligand which binds to the machinery associated with the ubiquitinating protein machinery. Also provided herein are methods of using these compounds in compositions or methods of treating patients with these compounds for the treatment of a disease or disorders such as cancer.

Abstract: Compositions and methods for treating melanoma are provided. Compositions include BRAFV600E-based peptides, alone or admixed with T helper peptides. Other compositions include nucleic acid sequences encoding the BRAFV600E-based peptides, alone or admixed with nucleic acid sequences T helper peptides. Dendritic cells pretreated with the BRAFV600E-based peptides, alone or admixed with T helper peptides, are also provided. These compositions are useful to treat melanoma, optionally co-administered with antibodies to checkpoint inhibitors or molecules that mimic the action of such antibodies.

Abstract: Chimeric protein constructs including a herpesvirus glycoprotein D (gD) and a heterologous polypeptide that interact with herpes virus entry mediator (HVEM) and enhance and enhance an immune response against the heterologous polypeptide and methods for their use are provided.

Abstract: In some embodiments, therapeutic treatments for a disease such as a cancer arc disclosed, including pharmaceutical compositions and methods of using pharmaceutical compositions for treating the cancer wherein the cancer cells overexpress arginine methyltransferase CARM1. In some embodiments, the therapeutic treatments disclosed include methods comprising the step of administering a therapeutically effective dose of an enhancer of zeste homolog 2 (EZH2) inhibitor to a subject, including a human subject, wherein the cancer cells of the subject overexpress arginine methyltransferase CARM1. In some embodiments, the EZH2 inhibitors are administered in conjunction with platinum-based antineoplastic drugs.

Abstract: A method of obtaining a population of cells enriched in human polymorphonuclear myeloid derived suppressor cells (PMN-MDSCs) comprises isolating from a cell suspension those cells which express LOX-1 to provide a population of cells enriched with PMN-MDSCs. A method of monitoring the population of LOX-1+ cells in a cell-containing biological sample is useful for determining the efficacy of treatment or the metastasis or increasing progression of cancer. Other cell isolation and diagnostic methods are also described.

Abstract: Methods and compositions are described for enhancing tissue regeneration or wound repair in a mammalian subject comprising a composition comprising (a) a proline hydroxylase inhibitor component or molecule that increases or upregulates HIF1a and (b) a carrier component comprising a hydrogel.

Abstract: In some embodiments, therapeutic treatments for a disease such as a cancer are disclosed, including pharmaceutical compositions and methods of using pharmaceutical compositions for treating the cancer wherein the cancer cells overexpress arginine methyltransferase CARM1. In some embodiments, the therapeutic treatments disclosed include methods comprising the step of administering a therapeutically effective dose of an enhancer of zeste homolog 2 (EZH2) inhibitor to a subject, including a human subject, wherein the cancer cells of the subject overexpress arginine methyltransferase CARM1. In some embodiments, the EZH2 inhibitors are administered in conjunction with platinum-based antineoplastic drugs.

Abstract: Targeting RAS is one of the greatest challenges in cancer therapy. Oncogenic mutations in NRAS are present in over 25% of melanomas and patients whose tumors harbor NRAS mutations have limited therapeutic options and poor prognosis. Thus far, there are no clinical agents available to effectively target NRAS or any other RAS oncogene. An alternative approach is to identify and target critical tumor vulnerabilities or non-oncogene addictions that are essential for tumor survival. The inventors investigated the consequences of NRAS blockade in NRAS-mutant melanoma and show that decreased expression of the telomerase catalytic subunit, TERT, is a major consequence. TERT silencing or treatment of NRAS-mutant melanoma with the telomerase-dependent telomere uncapping agent 6-thio-2?-deoxy-guanosine (6-thio-dG), led to rapid cell death, along with evidence of both telomeric and non-telomeric DNA damage, increased ROS levels, and upregulation of a mitochondrial anti-oxidant adaptive response.

Abstract: The present invention provides EBNA1 inhibitors, and/or pharmaceutical compositions comprising the same, that are useful for the treatment of diseases caused by EBNA1 activity, such as, but not limited to, cancer, infectious mononucleosis, chronic fatigue syndrome, multiple sclerosis, systemic lupus erythematosus and/or rheumatoid arthritis. The present invention further provides EBNA1 inhibitors, and/or pharmaceutical compositions comprising the same, that are useful for the treatment of diseases caused by latent Epstein-Barr Virus (EBV) infection and/or lytic EBV infection.

Abstract: The invention includes compositions and methods of generating a chimpanzee-derived adenovirus AdC6 or AdC7 vector vaccine comprising a deletion of E1, a deletion of E3 ORF3, ORF4, ORF5, ORF6, and ORF7 and a sequence encoding HIV protein gp140, gp160 or Gag, methods of treating and/or preventing or immunizing against HIV and methods of inducing an effector T cell, memory T cell and B cell immune response in a mammal administered the composition produced thereby. Furthermore, the invention encompasses a pharmaceutical composition for vaccinating a mammal as well as a protein expression system.

Abstract: This disclosure provides replication-incompetent adenoviral vectors useful in vaccine development and gene therapy. The disclosed vectors comprise a selective deletion of E3 and are particularly useful for preparation of vaccines development and for gene therapy using toxic transgene products that result in vector instability that occurs when the entire E3 domain is deleted.

Abstract: The present invention relates to methods and systems for high risk screening, diagnosis, prognosis, and surveillance of lung cancer. Accordingly, in one aspect, the invention provides a method for diagnosing or evaluating whether a subject has, or is at risk of having, lung cancer such as NSCLS. The method comprises obtaining a first expression level of the AKAP4 gene of a population of cells from the blood of a test subject; and comparing the first expression level with a first predetermined reference value. A difference between the first expression level and first predetermined reference value correlates with a diagnosis or evaluation of a lung cancer.

Abstract: Provided herein are methods of detecting a target nucleic acid sequence. In one embodiment, the method includes contacting genomic DNA with a guide RNA having a portion complementary to the target sequence in the genomic DNA and with Cas9 nickase to produce a single-strand break in the genomic DNA at a specific location adjacent to the target sequence. The method further includes contacting the nicked DNA with a polymerase and fluorescently labeled nucleotide. The fluorescently labeled nucleotide is incorporated into the nicked DNA at the specific location and the target nucleic acid sequence is detected via fluorescent label.

Abstract: Methods and compositions are provided for diagnosing lung cancer in a mammalian subject by use of 10 or more selected genes, e.g., a gene expression profile, from the blood of the subject which is characteristic of disease. The gene expression profile includes 10 or more genes of Table I or Table II herein.

Abstract: The present disclosure provide for methods of using 6-thio-2?-deoxyguanosine (6-thio-dG) to treat telomerase-positive cancers that exhibit (a) one or more TERT promoter mutations, and/or (b) enriched telomere transcriptional signature(s). In particular, melanomas, including those who are not sensitive or have become resistant to immune checkpoint inhibition and/or MAPKi therapy are targets for this therapy.

Abstract: This disclosure provides replication-incompetent adenoviral vectors useful in vaccine development and gene therapy. The disclosed vectors comprise a selective deletion of E3 and are particularly useful for preparation of vaccines development and for gene therapy using toxic transgene products that result in vector instability that occurs when the entire E3 domain is deleted.

Abstract: Compositions, e.g., therapeutic agents, and methods are provided for modulating gene and protein expression of Forkhead Box protein 1 (Foxp1). The therapeutic agents include short nucleic acid molecules that modulate gene and protein expression of Forkhead Box protein 1 (Foxp1) expression, viral vectors containing such molecules, T cells transduced with these viruses for adoptive therapies, and any small molecules that bind to and inactivate Foxp1. These compounds and methods have applications in cancer therapy either alone or in combination with other therapies that stimulate the endogenous immune system in the environment of the cancer, e.g., tumor.

Abstract: A diagnostic reagent or device comprises at least one ligand capable of specifically complexing with, binding to, or quantitatively detecting or identifying the biomarker chloride intracellular channel protein 4 (CLIC4) or an isoform, pro-form, modified molecular form including posttranslational modification, or unique peptide fragment or nucleic acid fragment thereof. An alternative diagnostic reagent or device comprises ligand or ligands capable of specifically complexing with, binding to, or quantitatively detecting or identifying multiple tropomyosin biomarkers. Optionally, such reagent or device includes a signaling molecule and/or a substrate on which the ligand is immobilized. Other reagents and methods of diagnosing ovarian cancer include use of CLIC4 ligands and/or multiple tropomyosin ligands with an additional ovarian cancer biomarker. For example, CLIC4 combined with one or more of CLIC1 and/or one or multiple members of the tropomyosin family, e.g.

Abstract: The present invention provides compositions and methods for treating cancer in a human. The invention relates to targeting the stromal cell population in a tumor microenvironment. For example, in one embodiment, the invention provides a composition that is targeted to fibroblast activation protein (FAP). The invention includes a chimeric antigen receptor (CAR) which comprises an anti-FAP domain, a transmembrane domain, and a CD3zeta signaling domain.

Abstract: Therapeutic treatments of a tumor expressing pT346 PDK1, including glioma expressing pT346 PDK1, are disclosed.