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.

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.

Provided herein are methods and compositions related to a method of stimulating the immune system in a subject in need thereof by administering an agent that increases the level or activity of indoleamine 2,3-dioxygenase (IDO1) and/or aryl hydrocarbon receptor (Ahr).

The present invention relates to combination therapies useful for the treatment of cancer. In particular, the invention relates to a therapeutic combination which comprises an anti-PD-L1 antibody and an IDO1 inhibitor. The therapeutic combination is particularly intended for use in treating a subject having a cancer that tests positive for PD-L1 or IDO1 expression.

The disclosure provides a composition for inhibiting the growth and/or invasion of tumor cells, an enhancer of an anti-tumor effect of a drug for the purpose of removing immunosuppression caused by cancer, or the like, which is characterized by being used for a specific subject.

The present application provides stable heterobiligands made up of peptide-based IDO1 ligands and small molecule inhibitors of IDO1 and methods of use of the heterobiligands as detection, imaging, diagnostic, and therapeutic agents. The application further provides methods of manufacturing IDO1 heterobiligands, capture agents, and imaging agents.

The present disclosure relates to one or more agents, therapies, treatments, and methods of use of the agents and/or therapies and/or treatments for upregulating production and/or functionality of one or more protein precursors of IDO-1, CTLA-4, PD-1, PD-L1, PD-L2 and INF-y. Embodiments of the present disclosure can be used as a therapy or a treatment for a subject that has a condition whereby the subject's immune system is or is likely to become, dysregulated and where the upregulation of these protein precursors may be of therapeutic benefit.

The invention provides antibodies that bind specifically to human indoleamine 2,3-dioxygenase 1 (IDO1), nucleic acids encoding the same, 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).

Provided herein are methods and compositions for treating cancer, including cancer that is not responsive to immunotherapy. In one aspect, the methods of treatment comprise administering to the subject a therapeutically effective amount of a -catenin inhibitor, a therapeutically effective amount of an IDO inhibitor, and a therapeutically effective amount of an immunotherapeutic agent. Another aspect is directed to pharmaceutical compositions comprising a -catenin inhibitor for use in treating cancer, wherein the composition is administered in combination with an IDO inhibitor and an immunotherapeutic agent. Yet another aspect is directed to a method of potentiating the therapeutic effect of immunotherapy against a cancer using a -catenin inhibitor, such as a -catenin nucleic acid inhibitor molecule, in combination with an IDO inhibitor.

The present invention is directed to compositions and methods to increase the expression of PD-L1 and/or IDO-1 in a population of cells, the modulated cells expressing increased PD-L1 and/or IDO-1, and methods related to the immunosuppressive effects obtained by cells expressing increased PD-L1 and/or IDO-1.