This disclosure provides for engineered T cell Receptors (TCRs), cells comprising the TCRs, and methods of making and using the TCRs. The current disclosure relates to TCRs that specifically recognize gp100. Accordingly, aspects of the disclosure relate to an engineered T-cell Receptors (TCRs), nucleic acids encoding the TCRs, and cells comprising the nucleic acids and TCRs. Also provided are compositions comprising the cells, nucleic acids, or engineered TCRs of the disclosure, methods of making the cells and methods of using the embodiments of the disclosure for therapeutic treatments.

The present invention provides an immunity-inducing agent comprising a polynucleotide-peptide conjugate or a pharmaceutically acceptable salt thereof as an active component, wherein the polynucleotide-peptide conjugate consists of: a single-chain polynucleotide or polynucleotide derivative comprising a CpG motif; a peptide; and a spacer which is covalently bonded at one end thereof to the polynucleotide or polynucleotide derivative and covalently bonded at the other end thereof to the peptide, wherein the peptide is a peptide modified by substituting one or more contiguous amino acids at the N-terminus of an MHC-binding peptide with an amino acid having a reactive functional group which allows for the formation of a covalent bond with the spacer, wherein the one or more contiguous amino acids contain no anchor residues for MHC binding.

The present invention provides a conjugate comprising an albumin binding peptide and a cargo, compositions for directing cargos to the lymphatic system, and vaccines. The methods of the invention can be used to increase an immune response, or to treat cancer or an infectious disease.

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.

The invention pertains to a method for treating a cancer which expresses PRAME using T cells which recognize specific peptide epitopes of PRAME, to a method for producing T cells that target cancer cells expressing PRAME, the peptide epitopes of PRAME themselves and to compositions and methods of treatment using these peptides.

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.

The present invention relates to a pharmaceutical composition comprising a modified mRNA that is stabilised by sequence modifications and optimised for translation. The pharmaceutical composition according to the invention is particularly well suited for use as an inoculating agent, as well as a therapeutic agent for tissue regeneration. In addition, a process is described for determining sequence modifications that promote stabilisation and translational efficiency of modified mRNA of the invention.

Cell-based compositions and methods for targeting and treating human diseases, including cancers and infectious diseases, are provided, wherein exogenous intracellular sarcosine is used for improved delivery of the composition.

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.