This invention relates to the treatment of cancer in an individual by administration of a population of modified T cells that express a recombinant cAMP phosphodiesterase (PDE) or a fragment thereof and an antigen receptor which binds specifically to cancer cells in the individual. Populations of modified T cells and methods of producing populations of modified T cells are provided, along with pharmaceutical compositions and methods of treatment

Nervous system trauma and neurodegeneration including in optic neuropathies are treated by administration of an effective dose of a PDE4D3 displacing agent to promote neurite extension, neuroprotection and recovery. In some embodiments the neurons are optic neurons, including without limitation retinal ganglion cells (RGCs). A cAMP signaling compartment restricted by mAKAPα-anchored PDE4D3 directly regulates neuronal phenotype, and can be molecularly manipulated with therapeutic effect.

Provided are methods of treating epilepsy. The methods include administering to an individual having epilepsy a therapeutically effective amount of a phosphodiesterase 4 (PDE4) inhibitor. Also provided are methods of identifying an anti-epileptic agent. Such methods include contacting a PDE4 polypeptide with a candidate agent in a PDE4 activity assay, where inhibition of activity of the PDE4 polypeptide by the candidate agent identifies the candidate agent as an anti-epileptic agent.

The present invention features, inter alia, pharmaceutical compositions and their use in the preparation of a medicament (e.g., a medicament for inflammation, such as an inflammatory lung disease) or in a therapeutic regimen. The compositions can include at least two active agents: a first agent that inhibits PDE4 (e.g., roflumilast) and a second active agent that inhibits the expression or activity of one or more PDE4B variants (e.g., PDE4B2). The compositions and methods will attenuate an unwanted up-regulation of a PDE4B (e.g., PDE4B2) and may thereby improve treatment with the first agent (e.g., roflumilast). For example, the second agent may improve the efficacy of the first agent, decrease the effective dose of the first agent, ameliorate the tolerance to the first agent that would otherwise develop (e.g., in patients with COPD exacerbation), reduce unwanted side effects caused by the first agent, or otherwise improve treatment regimes including a PDE4 inhibitor.

This invention relates to the treatment of cancer in an individual by administration of a population of modified T cells that express a recombinant cAMP phosphodiesterase (PDE) or a fragment thereof and an antigen receptor which binds specifically to cancer cells in the individual. Populations of modified T cells and methods of producing populations of modified T cells are provided, along with pharmaceutical compositions and methods of treatment.

Compounds of Formula (I), which are activators of long form cyclic nucleotide phosphodiesterase-4 (PDE4) enzymes, are provided. Methods and uses of these compounds for the treatment or prevention of disorders requiring a reduction of second messenger responses mediated by cyclic 3,5-adenosine monophosphate (cAMP) are also described.

This invention relates to the treatment of cancer in an individual by administration of a population of modified T cells that express a recombinant cAMP phosphodiesterase (PDE) or a fragment thereof and an antigen receptor which binds specifically to cancer cells in the individual. Populations of modified T cells and methods of producing populations of modified T cells are provided, along with pharmaceutical compositions and methods of treatment.

This invention relates to the treatment of cancer in an individual by administration of a population of modified T cells that express a recombinant cAMP phosphodiesterase (PDE) or a fragment thereof and an antigen receptor which binds specifically to cancer cells in the individual. Populations of modified T cells and methods of producing populations of modified T cells are provided, along with pharmaceutical compositions and methods of treatment.

The present disclosure relates to a genetically modified host cell having increased production of one or more vitamin B compounds, wherein the host cell is genetically modified by mutating one or more native polynucleotide constructs for reducing formation of a CRP-cAMP complex in the host cell and/or introducing one or more genetic alterations increasing the degradation and/or non-CRP binding of cAMP in the host cell; whereby the production of the vitamin B compound in the genetically modified host cell is increased compared to a parent host cell.

Compounds of Formula (I), which are activators of long form cyclic nucleotide phosphodiesterase-4 (PDE4) enzymes, are provided. Methods and uses of these compounds for the treatment or prevention of disorders requiring a reduction of second messenger responses mediated by cyclic 3,5-adenosine monophosphate (cAMP) are also described.

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