This invention relates to the use of a LAG-3 protein or a derivative thereof and optionally a chemotherapy agent for the treatment of cancer in a subject. The subject may have one or more of a low monocyte count, a Luminal B breast cancer, an age of less than about 85 years, has been previously treated with a CDK4/6 inhibitor, and has not previously undergone treatment with a taxane chemotherapy. Suitably, the cancer is a breast cancer, such as a hormone receptor positive breast cancer.

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.

Embodiments of the disclosure include methods and compositions for inhibiting the immune suppressive tumor microenvironment using cell therapy wherein the cells express a chimeric protein having an extracellular domain that binds TRAIL-R2 and an intracellular domain that in specific embodiments comprises one or more costimulatory domains that enhance activity of the cells upon activation. In specific embodiments, the chimeric protein comprises an scFv that targets TRAIL-R2 and an intracellular region that comprises a costimulatory domain from 4-1BB. In particular embodiments, the cells also express a therapeutic protein, such as a chimeric antigen receptor.

The present document relates to methods and materials for treating a subject having an autoimmune disease.

The application relates to a method of treating cancer or a tumor comprising administering a dual cytokine fusion protein composition, pharmaceutical composition, and/or formulation thereof comprising IL-10 or IL-10 variant molecules fused to a single chain variable fragment scaffolding system and a second cytokine, where the second cytokine is linked in the hinge region of the scFv, in combination with an adaptive cell therapies or bispecific T cell engagers.

The present application relates to the administration of plasma, fractions thereof, or mixtures thereof to humans or animals to treat or otherwise improve cognitive impairment disorders, including dementia (e.g., vascular dementia, dementia with Lewy bodies, dementia resulting from Alzheimer's disease, dementia resulting from Parkinson's disease, frontotemporal dementia, and dementia resulting from normal pressure hydrocephalus in humans, and cognitive dysfunction syndrome in companion animals), concussion, and traumatic brain injury. In certain embodiments, the invention comprises a method of treating a cognitive impairment disorder in a human or companion animal subject, said method comprising: administering to said subject one or more cognitive functioning tests to identify a subject suffering from a cognitive impairment disorder; and administering to said subject a therapeutically effective amount of an animal plasma composition; wherein said administration provides an improvement in said subject's results in said one or more cognitive impairment tests.

Disclosed are compositions of lipid nanoparticles (LNP) comprising an ionizable cationic lipid, a phospholipid, a sterol, and a PEG-lipid (non-functionalized and optionally functionalized). The functionalized PEG-lipid can be conjugated with a binding moiety to create a targeted LNP (tLNP). The disclosed tLNP preferentially deliver a nucleic acid molecule or other negatively charged payload to cells expressing a cell surface antigen recognized by the binding moiety of the tLNP, and are better tolerated, as compared to LNPs and tLNPs comprising ionizable cationic lipids found in marketed pharmaceuticals comprising LNPs.

Provided herein are, inter alia, nucleic acid-peptide conjugates including a non-cell penetrating protein attached at its C-terminus to a phosphorothioate nucleic acid. Attachment of the phosphorothioate nucleic acid to the non-cell penetrating protein conveys stability to and allows for efficient intracellular delivery of the non-cell penetrating peptide. The nucleic acid-peptide conjugates provided herein including embodiments thereof are useful, inter alia, for the treatment of cancer, inflammatory disease, pain, and viral infection.

Embodiments of the disclosure provide methods and compositions that facilitate cancer treatment including at least because they concern therapies that circumvent the tumor microenvironment. In specific embodiments, compositions are utilized for therapy that utilize tumor-infiltrating lymphocytes and/or engineered T cells that are protected from immunosuppression from the tumor microenvironment because they are engineered to have reduced or eliminated expression of transforming growth factor-beta receptor 2 and/or I-cell-Ig-and-ITIM-domain and/or CD7 genes.

The invention provides compositions and methods for treating diseases associated with expression of a cancer associated antigen as described herein. The invention also relates to chimeric antigen receptor (CAR) specific to a cancer associated antigen as described herein, vectors encoding the same, and recombinant T cells comprising the CARs of the present invention. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises an antigen binding domain that binds to a cancer associated antigen as described herein. The CAR may comprise a mutant CD28 costimulatory domain.