This disclosure features compositions comprising niclosamide for use in treating one or more conditions (or one or more symptoms thereof) characterized by an abnormal inflammatory response in one or more particular subject (e.g., patient) populations in need thereof. Such conditions include, e.g., an autoimmune disorder, e.g., colitis, e.g., autoimmune colitis, e.g, an inflammatory bowel disease, e.g., Crohn's disease, ulcerative colitis. In some embodiments, the uses include rectally (e.g., via enema) administering niclosamide.

Described herein are bispecific antibodies simultaneously targeting both CHI3L1 and the immune checkpoint molecule CTLA4. These antibodies manifest enhanced synergistic cytotoxic effects compared to the effects of individual CHI3L1 and CTLA4 antibodies, alone or in combination. Methods of treating tumors, including lung and brain tumors by administering the bispecific antibodies described herein are also provided.

Described herein are bispecific antibodies simultaneously targeting both CHI3L1 and the immune checkpoint molecule CTLA4. These antibodies manifest enhanced synergistic cytotoxic effects compared to the effects of individual CHI3L1 and CTLA4 antibodies, alone or in combination. Methods of treating tumors, including lung and brain tumors by administering the bispecific antibodies described herein are also provided.

The present disclosure provides novel and improved IL-15 fusion proteins for use in the treatment of cancer and other disorders. In various embodiments, the fusion proteins of the invention have two functional domains: an IL-15/IL-15RαSushi domain (also referred to herein as an “IL-15/IL-15RαSushi complex”) and an antibody domain, each of which can take different forms, and configured such that the IL-15 is fused to the C-terminal of the antibody domain and co-expressed and non-covalently complexed with IL-15RαSushi. Importantly, the fusions proteins of the present invention address several of the limitations observed with the IL-15 therapeutics evaluated to date; specifically, the fusion proteins demonstrate extended the half-life of IL-15 in vivo, and demonstrate optimized preclinical activity compared to rIL-15 or related cytokine therapeutics.

The invention provides methods for treating a cancer, comprising administering to a subject in need thereof a therapeutically effective amount of a small molecule inhibitor of the PD-1/PD-L1 interaction or a pharmaceutically acceptable salt or prodrug thereof in combination with a therapeutically effective amount of an anti-PD-1 antibody, wherein the small molecule inhibitor of the PD-1/PD-L1 interaction is not a protein.

The invention provides methods for treating a cancer, comprising administering to a subject in need thereof a therapeutically effective amount of a small molecule inhibitor of the PD-1/PD-L1 interaction or a pharmaceutically acceptable salt or prodrug thereof in combination with a therapeutically effective amount of an anti-PD-1 antibody, wherein the small molecule inhibitor of the PD-1/PD-L1 interaction is not a protein.

The present disclosure relates to compositions comprising an aqueous solution of at least about 70% by weight water in combination with selected fatty acid salts and optionally an alcohol and/or a cooling sensate, as well as methods of using the same to treat symptoms of hot flashes. The fatty acid salts form fiber-like crystalline particles that together form a self-supporting mesh structure with voids, the aqueous solution being contained in the voids. When the composition is compressed above a critical stress, the mesh allows for the entrapped aqueous solution to be expressed.

The disclosure provides microbial compositions (e.g., compositions comprising one or more microbes or protein components thereof), that can be administered to subjects to confer beneficial effects. Disclosed compositions can, for example, be useful in reducing visceral hypersensitivity, or pain in response to colorectal distension.

Disulfide-Isomerase A4 (PDIA4) inhibitors and use thereof for inhibiting pancreatic β-cell pathogenesis and treating diabetes are disclosed. Drug candidates that inhibit PDIA4 with IC50 values ranging from 4 μM to 300 nM are identified. The compounds are highly active in augmenting insulin secretion from pancreatic β-cells. The representative compound No. 8 (4,5-dimethoxy-2-propiolamidobenzoic acid), alone or in combination with metformin, is effective in preserving pancreatic β-cell function, treating and/or reversing, returning blood glucose concentration to a normal level in a diabetic.

This disclosure relates to compounds that inhibit glutathione S-transferases (GSTs) and/or NAD(P)H:quinone oxidore-ductase 1 (NQO1) for uses in treating cancer. In certain embodiments, this disclosure relates to compositions and uses of N-(thia-zol-2-yl)-carboxamide derivatives such as a N-(5-nitrothiazol-2-yl)-carboxamide derivatives for treating cancer such as glioblastoma. In certain embodiments, this disclosure relates to pharmaceutical compositions comprising a N-(thiazol-2-yl)-carboxamide derivative such as a N-(5-nitrothiazol-2-yl)-carboxamide derivative which is a compound of formula (I), or derivative, prodrug or salt thereof and a pharmaceutically acceptable excipient, wherein X, R.sup.1, R.sup.2, and R.sup.3 substituents are reported herein.