The present disclosure relates to the field of cancer treatment and prevention. The present disclosure further relates to (a) a first immune checkpoint polypeptide or a polynucleotide encoding the same; (b) a second immune checkpoint polypeptide or a polynucleotide encoding the same; and (c) an immune checkpoint inhibitor. The disclosure also relates to compositions comprising one or more of (a), (b) and/or (c), methods of use, and kits comprising same. The disclosure also relates to methods for stratifying cancer patients and methods for monitoring the treatment response.

Methods and compositions for treating leukemia involving administering a therapeutically effective amount of an inhibitor of indoleamine 2,3 dioxygenase (IDO1). The leukemia may be is acute myeloid leukemia or acute lymphoid leukemia. The inhibitor can be a small molecule such as indiximod, epacadostat, BMS-986205, navoximod, PF-0684003, KHK2455 or LY3381916 or epacadostat. The inhibitor can be used alone or in conjunctions with other chemotherapeutic agents. IDO1 can also be inhibited using a CRISP-CAS system. The inhibitor can be administered orally, intravenously, intramuscularly, topically, arterially, or subcutaneously.

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.

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.

The disclosure features lipid nanoparticle (LNP) compositions comprising metabolic reprogramming molecules and membrane anchoring moieties and uses thereof. The LNP compositions of the present disclosure comprise mRNA therapeutics encoding metabolic reprogramming polypeptides, e.g., IDO or TDO and membrane anchoring moieties. The LNP compositions of the present disclosure can reprogram myeloid and/or dendritic cells, suppress T cells and/or induce immune tolerance in vivo.

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.

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.

The invention relates to the field of prophylaxis and therapy of cancer. Provided is a Indoleamine 2,3-dioxygenase (IDO) or peptide fragments hereof that are capable of eliciting anti-cancer immune responses. Specifically, the invention relates to the use of IDO or peptides derived herefrom 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. The invention also provides that the medicaments herein provided may be used in combination with cancer chemotherapy treatment. The invention further provides 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.

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).

The invention relates generally to the field of bone diseases. More specifically, the invention relates to methods and compositions for the treatment of osteoporosis and related disorders.