The present invention relates to RNA, particularly an immunostimulatory RNA (isRNA), a coding RNA or a combination thereof, for use in the treatment or prophylaxis of a disease, in particular a tumor and/or cancer disease. The present invention also provides pharmaceutical compositions, and a kit comprising the RNA(s). Further, the invention also comprises medical uses of the RNA(s) and compositions comprising the RNA(s).

Described herein are compositions and methods for treating cancer and autoimmune diseases.

Provided herein is a cell comprising a recombinant nucleic acid encoding a transmembrane protein that has an extracellular binding domain that specifically binds to a brain-selective extracellular antigen, e.g., MOG, CDH10, PTPRZ1 or NRCAM, wherein the cell does not comprise a nucleic acid encoding an antigen-specific therapeutic that binds to a killing antigen expressed by a glioblastoma.

The invention relates to the use of melanin, complexed with a peptide, in particular containing epitopes for use as an immunostimulatory composition, wherein the peptide that has been modified as to increase nucleophilicity.

Some embodiments of the present disclosure are directed to methods that include delivering to a subject a nucleic acid encoding an antigen, wherein the nucleic acid is delivered via a tumor-selective vehicle or via intratumoral injection, and delivering to the subject an immune cell expressing a receptor that binds to the antigen.

The invention provides compositions and methods improved CAR T cell therapies. Specifically, the invention provides cells with reduced Tet, e.g., Tet2 function or expression, and methods of use therefore. The invention further provides Tet2 inhibitors and methods of use therefore in connection with CAR T cells.

The present invention includes compositions and methods for modifying a T cell with a nucleic acid encoding a switch molecule comprising an extracellular domain comprising a membrane receptor or fragment thereof and an intracellular domain comprising a signaling receptor or fragment thereof. In one aspect, a method comprises introducing a nucleic acid encoding a switch molecule and a nucleic acid encoding a soluble fusion protein and/or a nucleic acid encoding a bispecific antibody into a population of cells comprising T cells, wherein the T cells transiently expresses the switch molecule and soluble fusion protein or bispecific antibody. In other aspect, compositions of T cells and methods of treating a disease or condition, such as cancer or an autoimmune disease, are also included.

In various embodiments methods of producing a cell population enriched for CLEC9A+ dendritic cells are provided where the methods involve culturing stem cells and/or progenitor cells in a cell culture comprising culture medium, a notch ligand, stem cell factor (SCF), FLT3 ligand (FLT3L); thrombopoietin (TPO); and IL-3 and/or GMCSF.

Provided herein are cancer stem cell targeted cancer vaccines and methods for treating and vaccinating against cancer. Also contained herein are regimens by which cancer stem cell targeted cancer vaccines are administered, such regimens comprising peptides, compositions, immunomodulatory agents, and emulsifiers. Also provided are the patient populations to which the regimens are to be administered, and the dosages, schedules, route of administration for the regimens.

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.