Heterocyclic entities that modulate PI3 kinase activity, pharmaceutical compositions containing the heterocyclic entities, and methods of using these chemical entities for treating diseases and conditions associated with PI3 kinase activity are described herein.

The present invention relates to compounds and compositions for the inhibition of NAMPT, their synthesis, applications and antidotes. An illustrative compound of the invention is shown below: ##STR00001##

Provided herein are methods of treating graft-versus-host disease in a subject by administering pharmaceutical compositions containing bacterial strains of the Clostridia class. Also described herein are exemplary human-derived bacteria belonging to the Clostridia class, combinations of which have been shown to induce accumulation of regulatory T cells (Treg cells) in the colon and suppress immune functions, and are therefore useful for mitigating pathological immune responses. Pharmaceutical compositions containing these and/or related bacteria can be used to prevent and treat immune-mediated diseases such as graft-versus-host disease.

Antibodies and antigen binding fragments thereof are provided that bind to T-cell receptors (e.g., TCRα), essentially independent of T-cell epitope specificity. Methods for manipulation of T-cells and methods of treatment using such antibodies are likewise provided.

The present invention relates to, inter alia, compositions and methods, including chimeric proteins that find use in the treatment of disease, such as immunotherapies for cancer and autoimmunity. In part, the invention provides, in various embodiments, fusions of extracellular domains of transmembrane proteins that can have stimulatory or inhibitory effects.

The invention is directed to substituted piperidine derivatives. Specifically, the invention is directed to compounds according to Formula IIII: ##STR00001##
wherein A, B, X, Y, L.sup.1, L.sup.2, L.sup.3, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.9, z.sup.2, z.sup.4, z.sup.5, and z.sup.6 are as defined herein, and salts thereof. The compounds of the invention are inhibitors of the ATF4 pathway and can be useful in the treatment of cancer, pre-cancerous syndromes and diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, diabetes, Parkinson disease, Huntington's disease, Creutzfeldt-Jakob Disease, and related prion diseases, progressive supranuclear palsy, amyotrophic lateral sclerosis, myocardial infarction, cardiovascular disease, inflammation, fibrosis, chronic and acute diseases of the liver, chronic and acute diseases of the lung, chronic and acute diseases of the kidney, chronic traumatic encephalopathy (CTE), neurodegeneration, dementia, cognitive impairment, atherosclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting the ATF4 pathway and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

The present invention relates to an immunogenic polypeptide comprising a multitude of papillomavirus (PV) L2 N-terminal peptides corresponding to amino acids 20 to 50 of the L2 polypeptide of HPV16, wherein said HPV L2 N-terminal peptides are L2 N-terminal peptides from at least four different cutaneous HPV genotypes; and to the aforesaid immunogenic polypeptide for use in medicine and for use in vaccination of a subject against cutaneous HPV infection and/or mucosal HPV infection. The present invention further relates to a polynucleotide encoding the aforesaid immunogenic polypeptide and to vectors, host cells, methods for producing an antibody, as well as antibodies related thereto.

The present invention relates to an immunogenic polypeptide comprising a multitude of papillomavirus (PV) L2 N-terminal peptides corresponding to amino acids 20 to 50 of the L2 polypeptide of HPV16, wherein said HPV L2 N-terminal peptides are L2 N-terminal peptides from at least four different cutaneous HPV genotypes; and to the aforesaid immunogenic polypeptide for use in medicine and for use in vaccination of a subject against cutaneous HPV infection and/or mucosal HPV infection. The present invention further relates to a polynucleotide encoding the aforesaid immunogenic polypeptide and to vectors, host cells, methods for producing an antibody, as well as antibodies related thereto.

Provided herein are transplantation methods and methods of treating an inflammatory condition, ischemia reperfusion injury, infection, or a wound in a patient, comprising administering isolated IL-33 matrix-bound vesicles to the patient, as well as in vitro-expanded Treg cells. Also provided is a kit comprising IL-33 matrix-bound vesicles and in vitro-expanded Treg cells.

Provided herein are transplantation methods and methods of treating an inflammatory condition, ischemia reperfusion injury, infection, or a wound in a patient, comprising administering isolated IL-33 matrix-bound vesicles to the patient, as well as in vitro-expanded Treg cells. Also provided is a kit comprising IL-33 matrix-bound vesicles and in vitro-expanded Treg cells.