The present invention relates to a novel protein secretion factor, a vector including a nucleic acid sequence encoding the protein secretion factor, and a transformed cell into which the vector is introduced. The invention also relates to a method of producing a target protein using the transformed cell including the vector.

A trifunctional molecule is provided, comprising (i) a target-specific ligand, (ii) a ligand that binds a protein associated with a TCR complex, and (iii) a T cell receptor signaling domain polypeptide. Variants of the molecule are provided, including variants that exhibit optimized surface expression, transduction efficiency, and effector functionality. Variations include, for example, different ligands that bind CD3 epsilon (e.g., OKT3, L2K, F6A, UCHT1 and humanized UCHT1), different signaling domains, and different linkers between domains.

Described herein are agents that inhibit CBL autoinhibition, agents that activate CBL, SLAP and/or SLAP2 mimetics, and recombinant SLAP and/or SLAP2 or variants and/or fragments thereof that inhibit CBL autoinhibition. Also described are fusion proteins comprising these molecules as well as methods of inhibiting CBL autoinhibition and related uses thereof.

Disclosed herein relates to immunotherapeutic compositions comprising immunotherapeutic peptides comprising neoepitopes, polynucleotides encoding the immunotherapeutic peptides, antigen presenting cells comprising the immunotherapeutic peptides or polynucleotides, or T cell receptors specific for the neoepitopes. Also disclosed herein is use of the immunotherapeutic compositions.

Disclosed herein include methods, compositions, and kits suitable for use in detecting the activation level of a signal transducer. In some embodiments, there are provided synthetic protein circuits wherein recruitment of synthetic protein circuit components to an association location upon activation of a signal transducer generates an active effector protein. The effector protein can be configured to carry out a variety of functions when in an active state, such as, for example, inducing cell death. Methods of treating a disease or disorder characterized by aberrant signaling are provided in some embodiments.

Described are means of generating immunological compositions that are universally applicable for induction of immunity to neoplasia regardless of histological origin of tissue. Certain methods concern fibroblasts that are manipulated or dedifferentiated in a manner to induce expression of tumor associated antigens including cancer testis antigens. These cells are used as a source of antigenic stimuli for creation of a cellular vaccine, and/or an exosome vaccine, and/or a lysate-based vaccine.

The present invention relates to methods for treating patients having cancer or a premalignant or neoplastic condition. It is based, at least in part, on the discovery that a genome editing technique that specifically targets a fusion gene can induce cell death in a cancer cell other than a prostate cancer cell, e.g., a hepatocellular cancer cell, having the fusion gene. The present invention provides methods for treating cancer patients that include performing a genome editing technique targeting a fusion gene present within one or more cells of a subject to produce an anti-cancer effect.

The present disclosure relates generally to disruption of genomic complexes associated with fusion genes via a disrupting agent comprising a targeting moiety and/or an effector, e.g., disrupting, moiety. Described herein are experiments directed at identifying target anchor sequences proximal to fusion genes, e.g., fusion oncogenes; targeting the genomic complexes, e.g., CFLs, comprising said target anchor sequences for disruption (e.g., inhibiting their formation and/or destabilizing them) using disrupting agents; and evaluating the effects of disruption on fusion gene expression and other cell (e.g., cancer cell) characteristics (e.g., growth, viability, etc.).

The present disclosure relates generally to disruption of genomic complexes associated with fusion genes via a disrupting agent comprising a targeting moiety and/or an effector, e.g., disrupting, moiety. Described herein are experiments directed at identifying target anchor sequences proximal to fusion genes, e.g., fusion oncogenes; targeting the genomic complexes, e.g., CFLs, comprising said target anchor sequences for disruption (e.g., inhibiting their formation and/or destabilizing them) using disrupting agents; and evaluating the effects of disruption on fusion gene expression and other cell (e.g., cancer cell) characteristics (e.g., growth, viability, etc.).

Provided are a polypeptide for tumor immunotherapy and use thereof. The polypeptide includes at least one polypeptide in a first peptide group, and optionally, at least one polypeptide in a second peptide group, the first peptide group includes polypeptides having amino acid sequences set forth in SEQ ID NO: 1 to SEQ ID NO: 6, and first derivative peptides thereof, and the second peptide group includes polypeptides having amino acid sequences set forth in SEQ ID NO: 7 to SEQ ID NO: 15, and second derivative peptides thereof. Further provided are an isolated nucleic acid, a construct, an expression vector, a host cell, a pharmaceutical composition, an antigen-presenting cell, an immune effector cell, a tumor vaccine, use of the polypeptide in the preparation of drugs for preventing or treating tumors, and a method for treating a patient suffering from tumors.