The present invention provides an antibody against glypican-3 (GPC3) and application thereof, and the antibody comprises a single chain antibody and humanized antibody.

Provided herein are methods and articles of manufacture for use with cell therapy for the treatment of diseases or conditions, e.g., cancer, including for predicting and treating a toxicity. In some embodiments, the toxicity is related to cytokine release syndrome (CRS). The methods generally involve assessing a change in a factor indicative of tumor burden in a subject that is associated with and/or correlate to a risk of developing toxicity. In some aspects, the methods can be used to determine if the subject is at risk or likely at risk for developing a toxicity following administration of the cell therapy. Also provided are methods for treating a subject having a disease or condition, in some cases involving administration of the cell therapy, based on assessment of risk of developing a toxicity following administration of the therapy. Also provided herein are reagents and kits for performing the methods.

The present disclosure relates to EGFR-derived polypeptides containing short juxtamembrane sequences, nucleic acids encoding them, and methods of using them to improve cell surface expression of truncated EGFR markers.

Aspects of the present disclosure are directed to INCENP-targeting polypeptides, including antibodies, antibody-drug conjugates, antibody fragments, antibody-like molecules, and chimeric receptors. Also disclosed herein are nucleic acids encoding for such INCENP-targeting polypeptides and cells comprising such nucleic acids. Described are methods for detection, diagnosis, and treatment of cancer using INCENP-targeting polypeptides.

Production and use of novel therapeutic cells, called T-Vehicles, in the allogeneic Adoptive Cell Therapy setting allows a wide range of therapeutic benefits to accrue with minimal or no risk of GVHD. T-Vehicles are created from donor T cells that are altered to contain therapeutic attributes that do not include their native antigen receptors and can deliver therapeutic benefits irrelevant of their native antigen specificity. T-Vehicles can possess highly restricted native antigen specificity that renders them unable to recognize antigens present on normal cells and incapable of initiating GVHD, making them ideal transport vehicles to deliver various therapeutic attributes in vivo. In essence, production and use of T-Vehicles is a paradigm shift that opens the door to therapeutic application of T cells in ways not previously contemplated, independent of whether or not there is an HLA match between the donor and the recipient.

The present application provides single-domain antibodies targeting BCMA, and chimeric antigen receptors (such as monovalent CAR, and multivalent CAR including bi-epitope CAR) comprising one or more anti-BCMA single-domain antibodies. Further provided are engineered immune effector cells (such as T cells) comprising the chimeric antigen receptors. Pharmaceutical compositions, kits and methods of treating cancer are also provided.

The present invention relates to a cell which co-expresses: (i) a first chimeric antigen receptor (CAR) at the cell surface, comprising an antigen-binding domain which binds to CD19; (ii) a second CAR at the cell surface, comprising an antigen-binding domain which binds to CD22; (iii) dominant negative SHP2 (dSHP2); and (iv) dominant negative TGF receptor II (dnTGFRII).

The invention relates to a nucleic acid encoding, an artificial T cell receptor, or a fragment of an artificial T cell receptor, wherein the nucleic acid is operatively linked to a transcriptional regulatory sequence, and wherein the transcriptional regulatory sequence comprises a binding domain for a transcription factor that promotes a regulatory T lymphocyte phenotype and cells comprising such nucleic acids. The cells may further comprise a nucleic acid encoding the transcription factor and a targeting polypeptide. The cells of the invention are useful in medicine, in particular in the treatment of inflammatory conditions.

The current application fulfills a need for methods of making bi-specific CAR T-cells that have high efficacy. Aspects of the disclosure relate to a method for manufacturing a CD19/CD20 bi-specific chimeric antigen receptor (CAR) T cell comprising the ordered steps of: (a) providing a composition comprising a population of cells comprising T cells; (b) contacting the composition comprising the population of cells comprising T cells with one or more of a transactivating composition, IL-2, and/or IL-15; (c) transducing the cell composition from (b) with a CD19/CD20 bi-specific CAR nucleic acid; and (d) removing the transactivating composition from the cell composition of (c). Further aspects relate to a population of CD19/CD20 bi-specific CAR-T cells produced by the methods of the disclosure. Yet further aspects describe a method for treating a subject for B-cell lymphoma comprising administering cells of the disclosure.

Provided are anti-GPC3 antibodies, including murine antibodies, humanized antibodies, and those with further optimized CDR sequences. The antibodies exhibited higher cell-based binding efficiency than the leading anti-GPC3 antibody candidate under clinical development.