A peptide nucleic acid derivative of Formula I is provided to tightly bind to a splice site within a pre-mRNA in a sequence specific manner. Given with excellent cell membrane permeability and strong affinity for RNA, the said peptide nucleic acid derivative induces exon skipping in cells treated with the peptide nucleic acid at sub-femtomolar concentration as naked oligonucleotide. The said compound shows therapeutic activity in subjects upon systemic administration even at 1 g/Kg or less, and therefore is useful to treat a disease or symptom at affordable treatment cost.

The invention provides antibodies that bind specifically to human indoleamine 2,3-dioxygenase 1 (IDO1), and methods of using the same. The antibodies are capable of binding to a sequence comprising SEQ ID NO: 1 and specifically bind to human IDO1 in formalin fixed paraffin embedded tissues. The antibodies are useful in a number of different analytical techniques, including immunohistochemistry (IHC) and immunocytochemistry (ICC).

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.

Provided herein are targeted effector fusion proteins, complexes thereof, and uses thereof. The targeted effector fusion proteins can include an effector protein that can be linked to a targeting moiety. Monomer targeted effector fusion proteins can form homogeneous or heterogeneous complexes. The targeted effector fusion proteins and complexes thereof can be formulated as pharmaceutical formulations. The targeted effector fusion proteins, complexes thereof, and formulations thereof can be administered to a subject in need thereof.

The present invention relates to the field of prophylaxis and therapy of cancer. In particular there is provided a protein Indoleamine 2,3-dioxygenase (IDO) or peptide fragments here of that are capable of eliciting anti-cancer immune responses. Specifically, the invention relates to the use of IDO or peptides derived here from or IDO specific T-cells for treatment of cancer. The invention thus relates to an anti-cancer vaccine which optionally may be used in combination with other immunotherapies and to IDO specific T-cells adoptively transferred or induced in vivo by vaccination as a treatment of cancer. It is an aspect of the invention that the medicaments herein provided may be used in combination with cancer chemotherapy treatment. A further aspect relates to the prophylaxis and therapy of infections by the same means as described above.

The use of IDO and immunogenic peptide fragments hereof in cancer and infection treatment, diagnosis and prognosis is also provided.

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.

The present invention provides fusion proteins that induce local immune tolerance. The fusion proteins comprise peptides derived the immunoregulatory proteins programmed death ligand-1 (PD-L1) and indolamine 2,3-dioxygenase (IDO). Also provided are nucleic acid constructs encoding said fusion proteins, cells comprising said nucleic acid constructs, and methods of transplanting said cells into a subject.

Methods of treating B27-negative subjects having uveitis with an Inositol Polyphosphate Multikinase (IPMK) therapeutic agent and/or an Indoleamine 2,3-dioxygenase 2 (IDO2) agonist, and methods of identifying subjects having an increased risk of developing uveitis are described herein.

Blockade of immune checkpoints such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1) shows promise in patients with cancer. Inhibitory antibodies directed at these receptors have been shown to break immune tolerance and promote anti-tumor immunity. These agents work particularly well in patients with a certain category of tumor. Such tumors may be particularly susceptible to treatment because of the multitude of neoantigens which they produce.

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.