This invention relates to a method to modulate exogenous gene expression in which an ecdysone receptor complex comprising: a DNA binding domain; a ligand binding domain; a transactivation domain; and a ligand is contacted with a DNA construct comprising: the exogenous gene and a response element; wherein the exogenous gene is under the control of the response element and binding of the DNA binding domain to the response element in the presence of the ligand results in activation or suppression of the gene. The ligands comprise a class of ketones.

The present invention provides an isolated methyl degron peptide and a fusion protein comprising a methyl degron peptide. Also, the present invention provides screening methods for agents affecting protein lifespan and anti-cancer agents. Moreover, the present invention provides methods of controlling protein lifespan, regulating protein expression, and treating cancers by using a methyl degron peptide or a methyl degron gene.

The present invention provides a PPARδ activator containing a novel PPARδ agonist (peroxisome proliferator-activated receptor δ) as an active ingredient, and an exercise tolerance-improving agent containing the same as an active ingredient. The present invention is a PPARδ activator containing a guanidine derivative or a biguanidine derivative as an active ingredient, wherein the PPARδ activator activates transcriptional activity of PPARδ, and the guanidine derivative and the biguanidine derivative are capable of fitting within a PPARδ ligand binding pocket in a state where a guanidino group or a biguanidino group forms a hydrogen bond with amino acid residues corresponding to each of the 413th histidine, 287th histidine, 253rd threonine and the 437th tyrosine of human PPARδ, among amino acid residues constituting an interior surface of the ligand binding pocket; and is an exercise tolerance-improving agent containing the PPARδ activator as an active ingredient.

The present invention relates to therapeutic agents, particularly to therapeutic polypeptides and nucleic acids having the capacity for selective expression under conditions of hypoxia, cells incorporating the nucleic acids and their use in therapy, in particular in methods requiring selective expression under conditions of hypoxia, such as typically found in solid cancers. The nucleic acids encode novel hypoxia-responsive chimeric antigen receptors (CARs). The invention also relates to hypoxia-responsive regulatory nucleic acids.

The compositions described herein include an epitope of a peptide that may elicit an immune response in a subject following administration. The compositions may comprise nucleic acids. The compositions may comprise peptides. The methods described herein include administering a composition comprising an epitope of a peptide to a subject in need thereof.

Disclosed herein are improved methods for treatment of brain cancer (such as glioma/glioblastoma) via ligand-inducible gene-switch controlled in vivo expression of an immunomodulator (i.e., IL-12) in combination with one or more other immunomodulators (i.e., an immune cell check point inhibitor; e.g., such as a PD-1 inhibitor or a PD-1 binder.

Described herein is the finding that increasing the frequency of Zscan4 activation in mouse ES cells not only enhances, but also maintains their developmental potency in long-term cell culture. As the potency increases, even a whole animal can be produced from a single ES cell injected into a 4N blastocyst at an unexpectedly high success rate. The studies disclosed herein indicate that ES cells acquire higher potency by going through the transient Zscan4 activation state more frequently than the regular state. Particularly disclosed herein is the finding that the constitutive presence of Zscan4-ERT2, even in the absence of its usual activator tamoxifen, can increase the frequency of endogenous Zscan4 activation in ES cells, resulting in the increase of developmental potency of the ES cells. Accordingly, provided herein are Zscan4-ERT2 fusion proteins and nucleic acid molecules and vectors encoding Zscan4-ERT2 fusion proteins. Further provided are methods of prolonging and/or enhancing stem cell pluripotency using the disclosed Zscan4-ERT2 nucleic acid molecules and fusion proteins.

Disclosed herein are methods of increasing numbers of monocytes to a tumor or cancer metastasis site in a subject. Non-limiting embodiments include administering or using a Nur77 polypeptide or subsequence thereof; a Nur77 agonist; a CX3CR1 agonist; CD14.sup.+CD16.sup.+ monocytes and/or CD14.sup.dimCD16.sup.+ (CD115.sup.+CD11b.sup.+GR1.sup.− (Ly6C−)) monocytes; CD14.sup.+CD16.sup.+ monocytes and/or CD14.sup.dimCD16.sup.+ (CD115.sup.+CD11b.sup.+GR1.sup.− (Ly6C−)) monocytes contacted with a Nur77 agonist or contacted with a CX3CR1 agonist. Also disclosed herein are methods of increasing, stimulating, activating or promoting monocyte migration to or mobilization against a tumor or cancer metastasis in a subject. Non-limiting embodiments include administering a Nur77 polypeptide or subsequence thereof; a Nur77 agonist; a CX3CR1 agonist; CD14.sup.+CD16.sup.+ monocytes and/or CD14.sup.dimCD16.sup.+ (CD115.sup.+CD11b.sup.+GR1.sup.− (Ly6C−)) monocytes; or CD14.sup.+CD16.sup.+ monocytes and/or CD14.sup.dimCD16.sup.+ (CD115.sup.+CD111b.sup.+GR1.sup.− (Ly6C−)) monocytes contacted with a Nur77 agonist or contacted with a CX3CR1 agonist.

The present invention relates to a pharmaceutical composition comprising a LCoR activator and an immune checkpoint inhibitor (ICI), to its use in the treatment of cancer and to the use of LCoR as marker of response to immunotherapy in cancer treatment.

The present invention provides a novel protein and biologically-active fragments and variants thereof with advantageous therapeutic and cosmetic uses. Also provided are methods of using the proteins, as well as methods of producing the proteins using a recombinant cell. Further provided are recombinant host cells transformed with a polynucleotide sequence that encodes the expression of the proteins.