Compositions and methods for the treatment of cancer are described, and, more preferably, to the treatment of cancers that do not express, or are otherwise deficient in, argininosuccinate synthetase, with enzymes that deplete L-Arginine in serum. In one embodiment, the present invention contemplates an arginase protein, such as a human Arginase I protein, comprising at least one amino acid substitution and a metal cofactor, said protein comprising an increased catalytic activity when compared with a native human Arginase I.

In one embodiment, a single modality cancer immunotherapy regimen that includes a therapeutic composition is provided. Such a therapeutic composition may include a Salmonella strain comprising a plasmid that expresses an shRNA molecule that suppresses the expression of an immunosuppressive target and suppresses tumor growth. In some aspects, the Salmonella strain is an attenuated Salmonella typhimurium strain. In other aspects, the immunosuppressive target is STAT3, IDO1, IDO2, Arginase 1, iNOS, CTLA-4, TGF-?, IL-10, pGE2 or VEGF. In one embodiment, the immunosuppressive target is IDO1 or Arg1 and the shRNA molecule is any one of SEQ ID NO:5-14.

One example embodiment is a method of treating lung carcinoma in a subject in need thereof. The method includes administering to the subject a therapeutically effective amount of an arginine reducing compound and a therapeutically effective amount of an ornithine decarboxylase (ODC) inhibitor to provide a combination therapy that has a synergistic therapeutic effect compared to an effect of the arginine reducing compound and an effect of the ODC inhibitor, in which each of the arginine reducing compound and the ODC inhibitor is administered alone.

Disclosed herein are novel compounds, pharmaceutical compositions comprising such compounds and related methods of their use. The compounds described herein are useful, e.g., as liposomal delivery vehicles to facilitate the delivery of encapsulated polynucleotides to target cells and subsequent transfection of said target cells, and in certain embodiments are characterized as having one or more properties that afford such compounds advantages relative to other similarly classified lipids.

Methods of treating tumors or cancer include administration of an arginine depleting enzyme and an immune-oncology agent.

Disclosed herein are novel compounds, pharmaceutical compositions comprising such compounds and related methods of their use. The compounds described herein are useful, e.g., as liposomal delivery vehicles to facilitate the delivery of encapsulated polynucleotides to target cells and subsequent iransfection of said target cells, and in certain embodiments are characterized as having one or more properties that afford such compounds advantages relative to other similarly classified lipids.

The present invention relates to the provision of genetically modified microbial cells, such as yeast cells with an improved ability for producing L-ornithine and its derivatives. Overproduction of L-ornithine is obtained in the first place by the down-regulation or attenuation of specially selected genes, wherein said genes encode enzymes involved in the L-ornithine consumption and/or degradation pathways. Further L-ornithine production ability is improved by down-regulation, attenuation, deletion or overexpression of specially selected genes, wherein said genes encode enzymes and/or proteins involved in the L-ornithine acetylated derivatives cycle, L-glutamate synthesis pathways, subcellular trafficking, TCA cycle, pyruvate carboxylation pathway, respiratory electron-transport chain, and the carbon substrates' assimilation machinery. The invention additionally provides a method to produce L-ornithine with said modified eukaryotic cells.

A nanoplatform assembly for detection of arginase, indoleamine 2,3-dioxygenase 1, and/or tryptophan 2,3-dioxygenase. The nanoplatform comprises an oligopeptide, which is used as a linker between two particles. More preferably, the linker is comprised of an oligopeptide containing a substrate for the target enzyme, where the substrate is chemically or physically modified by the target enzyme (but not cleaved). A central particle with a plurality of oligopeptide-tethered detectable particles and a plurality of directly attached detectable particles is described. Posttranslational modification of the oligopeptide leads to changes in the detectable signals from the first and/or second particles in the nanoplatform, which can be correlated to enzyme activity and concentration.

Methods and compositions therefor of treating GAMT deficiency or guanidino acetate (GAA) toxicity in a subject comprising administration of an arginine depleting enzyme. An therapeutic formulation can include an arginase, an arginine deiminase or a combination thereof and optionally other compounds, and can be adapted for intravenous or subcutaneous administration to a subject.

Methods and compositions comprising recombinant Arginase I proteins which are capable of depleting the plasma arginine levels in a subject are disclosed. The methods and compositions can be used to modulate the activity of the immune system in a subject. Modulation of the immune system is useful in the treatment of immune disorders and in preventing rejection of a transplanted organ, tissue, or cell. The methods and compositions can also be used to treat a bone condition of a subject.