The present invention relates to methods of activate an isoform of protein kinase C (PKC) for the treatment of neurological diseases including Alzheimers disease and stroke using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids. The present invention also relates to methods of reducing neurodegeneration using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids.

Provided are methods of treatment involving immunotherapy, such as T cell therapy, and administration of a tryptophan metabolism and/or kynurenine pathway modulator. In some embodiments, the method includes a combination therapy that involves administration of engineered T cells, such as chimeric antigen receptor (CAR)-expressing cells, and a tryptophan metabolism and/or kynurenine pathway modulator, such as an inhibitor of an enzyme. Also provided are engineered cells in which the expression of a molecule involved in the kynurenine pathway is modified. Also provided are methods of manufacturing engineered cells, cells, compositions, methods of administration to subjects, nucleic acids and kits for use in the methods. In some aspects, features of the methods and cells provide for increased or improved activity, activity, outcome, function, response, persistence, expansion and/or proliferation of cells for adoptive cell therapy.

The invention pertains to a method of treating melanoma by administering to a subject in need thereof, a composition comprising a therapeutically effective amount of an inhibitor of PKC- and/or PKC-.Math.. Non-limiting examples of an inhibitor of PKC- and/or PKC-.Math. include ICA-1 and ACPD. The invention also provides PKC- and/or PKC-.Math. as biomarkers for identifying a melanoma in a subject as likely to be responsive or non-responsive to a therapy using an inhibitor of PKC- and/or PKC-.Math.. Accordingly, a method of identifying a subject having a melanoma as being responsive or non-responsive to a melanoma therapy with an inhibitor of PKC- and/or PKC-.Math. based on the levels and/or activity of PKC- and/or PKC-.Math. mRNA or protein in the melanoma cells from the subject are also provided.

Provided are methods of treatment involving immunotherapy, such as T cell therapy, and administration of a tryptophan metabolism and/or kynurenine pathway modulator. In some embodiments, the method includes a combination therapy that involves administration of engineered T cells, such as chimeric antigen receptor (CAR)-expressing cells, and a tryptophan metabolism and/or kynurenine pathway modulator, such as an inhibitor of an enzyme. Also provided are engineered cells in which the expression of a molecule involved in the kynurenine pathway is modified. Also provided are methods of manufacturing engineered cells, cells, compositions, methods of administration to subjects, nucleic acids and kits for use in the methods. In some aspects, features of the methods and cells provide for increased or improved activity, activity, outcome, function, response, persistence, expansion and/or proliferation of cells for adoptive cell therapy.

The present invention relates to methods of activate an isoform of protein kinase C (PKC) for the treatment of neurological diseases including Alzheimer's disease and stroke using cyclopropanated or epoxidized derivatives of mono- and polyunsaturted fatty acids. The present invention also relates to methods of reducing neurodegeneration using cyclopropanated or epoxidized derivatives of mono and polyunsaturated fatty acids.

The present invention relates to a method for identifying a target protein using a thermal stability shift-based fluorescence difference in two-dimensional gel electrophoresis, and more specifically, a method for identifying a protein, which is a target of a specific drug, by analyzing, by means of a fluorescence difference in two-dimensional gel electrophoresis, a thermal stability shift in the protein when a specific drug, preferably a bioactive molecule, binds to the target protein.

The present invention relates to methods of activate an isoform of protein kinase C (PKC) for the treatment of neurological diseases including Alzheimer's disease and stroke using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids. The present invention also relates to methods of reducing neurodegeneration using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids.

The present invention relates to a fusion protein consisting of a C2 domain and an Akt protein fragment, particularly the fragment consisting of the amino acid residues ranging from the 111.sup.th to the 480.sup.th amino acids from the N-terminus of the Akt protein, and a use of the said fusion protein. More specifically, the fusion protein of the present invention increases the Akt protein activity even under the condition of high calcium concentration, reduces body weight and fat in an animal model treated with a high fat diet infected with adenovirus containing the fusion protein above, improves insulin resistance and improves fatty liver, so that the fusion protein comprising the C2 domain and the fragment consisting of the amino acid residues ranging from the 111.sup.th to 480.sup.th amino acids from the N-terminus of Akt protein can be effectively used for the treatment of metabolic disease.

The invention provides to PKN1 gene fusions, PKN1 fusion proteins, and fragments of those genes and polypeptides. The invention further provides methods of diagnosing and treating diseases or disorders associated with PKN1 fusions, such as conditions mediated by aberrant PKN1 expression or activity, or over expression of PKN1.

The disclosed invention relates to methods of modifying peptide compositions to increase stability and delivery efficiency. Specifically, the disclosed invention relates to methods to increase the stability and delivery efficiency of protein kinase C (PKC) modulatory peptide compositions. A therapeutic peptide composition comprises a carrier peptide and a cargo peptide. A carrier peptide is a peptide or amino acid sequence within a peptide that facilitates the cellular uptake of the therapeutic peptide composition. The cargo peptide is a PKC modulatory peptide. Peptide modifications to either the carrier peptide, the cargo peptide, or both, which are described herein increase the stability and delivery efficiency of therapeutic peptide compositions by reducing disulfide bond exchange, physical stability, reducing proteolytic degradation, and increasing efficiency of cellular uptake.