The invention relates to protein-based T-cell receptor knockdown, and its use in T-cell therapies.

The present invention provides peptides useful as epitope tags, which may be fused to a polypeptide of interest, as well as antibodies that specifically bind to these peptides. The peptides and/or antibodies can be used for detecting, immobilizing, isolating or purifying a molecule that is conjugated to such a peptide and/or antibody.

The present disclosure provides a peptide tag, and a nucleic acid encoding the peptide tag. The peptide tag of the present disclosure can reduce an aggregation property of a protein in a cell. Specifically, the peptide tag of the present disclosure can be a peptide tag in which 5% or more and less than 45% of amino acids contained in an amino acid sequence thereof are acidic amino acids, and (b) 20% or more of the amino acids contained in the amino acid sequence are amino acids selected from the group consisting of F, P, Y, G, S, Q, N, and A.

The disclosure teaches antibodies that are useful, inter alia, in methods for detecting and treating human cancer. In a particular aspect, the disclosure teaches novel antibodies that are useful for detecting and treating human breast cancer. In some embodiments, the disclosure teaches novel antibodies that bind to filamin A. In some embodiments, the antibodies are intrabodies.

Disclosed herein are multifunctional polypeptides comprising an optional signal peptide sequence, a cell penetrating peptide, an antigen binding domain (e.g., anti-synuclein, anti-tau, anti-huntingtin), and a programmable proteasome-targeting PEST motif, and methods for using these polypeptides in treatment of protein aggregation diseases, e.g., neurodegenerative diseases.

The invention provides a method for inhibiting an intracellular target in a cell with a bispecific antibody comprising contacting the cell with a bispecific antibody having a first Fv fragment with a cell-penetrating determinant and a second Fv fragment with an intracellular target-binding determinant under suitable conditions so that the first Fv fragment causes the bispecific antibody to enter the cell and the second Fv fragment binds the intracellular target in the cell and thereby inhibiting the intracellular target.

This invention provides compositions and methods to prevent aberrant cell proliferation in a subject using a single-domain antibody (sdAb) directed against an intracellular component, wherein the aberrant cell proliferation can be cancer. The sdAb is synergistic with one or more chemotherapeutic drugs and improves therapeutic efficacy of the one or more chemotherapeutic drug against cancer. The invention also includes a method of treating viral infections using a sdAb, wherein the sbAb inhibits the replication of viruses such as Ebola virus and Zika virus in infected cells.

The present invention relates to chimeric receptors that can be used in whole-cell sensors for detecting analytes of interest. The inventors showed that the DNA binding domains and downstream gene expression can be activated via dimerization of an artificial dimerization composed of a single chain variable domain. They demonstrated for the first time that an artificial bacterial receptor using an antibody-like domain can be activated and produce a transcriptional output upon ligand-binding. In particular, the present invention relates to a chimeric receptor polypeptide comprising: i) a first DNA binding domain, ii) at least one binding domain selected from the group consisting of heavy chain variable domain, camelid VHHs, or antibody mimetics having specificity for an analyte, and iii) a linker between the DNA binding domain and the binding domain.

The efficacy and indication of dupilumab do not depend on the Fc region and are subject to transit across cell walls. They can be expanded by using their scFvs conjugated with N-methyl lobe of transferrin protein connected with an environment-sensitive cleavable linker to prevent exocytosis of the scFv yielding high exposure inside body cells such as in the brain, eye, and cancer cells that overexpress transferrin receptors.

The present invention provides a method for producing an exosome that transfers an active substance specifically to a target and the exosome produced by the same; a method for delivering the active substance to the target tissue using the exosome; a pharmaceutical composition for delivery of the active substance comprising the exosome as an active ingredient; and a composition for preparing the exosome comprising an expression vector wherein the target peptide is inserted into an extracellular portion of a transmembrane protein.