Abstract: The present application provides anti-LAG-3 constructs comprising a single-domain antibody (sdAb) that specifically recognizes LAG-3. Also provided are methods of making and using these constructs.

Abstract: Described herein are T cells engineered to express a chimeric antigen receptor (CAR), such as an anti-mesothelin CAR alone or in combination with a follicle-stimulating hormone receptor (FSHR) binding domain and/or a dominant negative transforming growth factor-? receptor II (dnTGF?RII) for the treatment of diseases associated with mesothelin expression. Also described are T cells engineered to express a modified T cell receptor (TCR).

Abstract: Provided are constructs comprising a single-domain antibody (sdAb) moiety that specifically recognizes TIGIT. Also provided are methods of making and using these constructs.

Abstract: Provided herein is a method of treating a subject who has multiple myeloma. A single infusion of chimeric antigen receptor (CAR)-T cells comprising an anti-BCMA CAR comprising a polypeptide is administered to the subject. In certain embodiments, the dose of CAR-T cells administered to the subject is from 1.0×105 to 5.0×106 of CAR-T cells per kilogram of the subject's mass. The method of treatment is effective in obtaining and maintaining minimal residual disease negativity status, as well as other beneficial clinical outcomes related to efficacy and safety.

Abstract: Provided is a chimeric antibody immune cell engager comprising a target cell binding domain that specifically binds to an antigen on a target cell, and an immune effector cell binding domain comprising an antigen-binding fragment that specifically binds to an antigen on an immune effector cell. Also provided are pharmaceutical compositions, kits and methods of treatment.

Abstract: Provided herein are methods of treating a subject who has multiple myeloma and has received prior treatment and has limited treatment options. Infusions of chimeric antigen receptor (CAR)-T cells comprising an anti-BCMA CAR comprising a polypeptide are administered to the subject. In certain embodiments, the dose of CAR-T cells administered to the subject is from 1.0 × 105 to 5.0 × 106 of CAR-T cells per kilogram of the subject’s mass. The method of treatment is effective in obtaining and maintaining minimal residual disease negativity status, as well as other beneficial clinical outcomes related to efficacy and safety.

Abstract: Provided herein are methods of treating a subject who has multiple myeloma with a ciltacabtagene autoleucel suspension. Also provided are pharmaceutical products containing ciltacabtagene autoleucel suspensions, instructions for use of the ciltacabtagene autoleucel suspensions, and methods for selling a drug product containing ciltacabtagene autoleucel suspensions.

Abstract: Provided are constructs comprising a single-domain antibody (sdAb) moiety that specifically recognizes PD-1. Also provided are methods of making and using these constructs.

Abstract: The present application provides an antibody, such as a monoclonal antibody (mAb), or an antigen binding fragment thereof, that specifically recognizes TIGIT. Also provided are pharmaceutical compositions, or methods of making and using the antibody or antigen-binding fragment thereof.

Abstract: Single domain antibodies that bind to Claudin18.2, and chimeric antigen receptors comprising same are provided. Further provided are engineered immune effector cells (such as T cells) comprising the chimeric antigen receptors. Pharmaceutical compositions, kits and methods of treating a disease or disorder are also provided.

Abstract: The present application provides constructs comprising a single-domain antibody (sdAb) moiety that specifically recognizes PD-L1. Also provided are methods of making and using these constructs.

Abstract: Provided are anti-glypican-3 (GPC3) antibodies or antigen binding fragments thereof, and a chimeric antigen receptor (CAR) that binds glypican-3 (GPC3) containing an anti-GPC3 antibody in an extracellular domain, a transmembrane domain, and an intracellular signaling domain. Immune effector cells transduced with the disclosed CAR constructs can be used for cancer immunotherapy.

Abstract: A modified T cell comprising a functional exogenous receptor is provided. The functional exogenous receptor comprises: (a) an extracellular ligand binding domain, (b) a transmembrane domain, and (c) an intracellular signaling domain (ISD) comprising a chimeric signaling domain (CMSD), wherein the CMSD comprises a plurality of Immune-receptor Tyrosine-based Activation Motifs (ITAMs) optionally connected by one or more linkers. Further provided are vectors, methods of producing, pharmaceutical compositions, kits, and methods of treatment thereof.

Abstract: A chimeric antigen receptor (CAR) comprising a polypeptide comprising an extracellular antigen binding domain comprising a first BCMA binding moiety and a second BCMA binding moiety, wherein the first BCMA binding moiety is a first anti-BCMA single domain antibody, and the second BCMA binding moiety is a second anti-BCMA sdAb; and wherein each of the first and second sdAb is a VHH domain.

Abstract: Disclosed herein is a novel chimeric antigen receptor and use thereof. The novel chimeric antigen receptor consists of a signal peptide, an antigen binding domain, a transmembrane region, and an intracellular signal domain, and comprises a 4-1BB signal peptide and/or a 4-1BB molecular transmembrane region. Nucleic acid sequences of various chimeric antigen receptors are separated and purified and provided is a chimeric antigen receptor and a CAR-T cell which are specific for a CD19 malignant tumor antigen. In the malignant tumor killing test of hematological cell lines, the ability of immune cells to target and recognize tumor cells is significantly enhanced, and the killing activity against tumor cells is also enhanced.

Abstract: Novel antibodies, such as single domain antibodies (sdAbs), or antigen-binding fragments thereof that specifically bind a transferrin are described. Compositions, methods and systems for increasing the half-life of a target protein in a serum using an antibody or fragment thereof against a transferrin are also described.

Abstract: The present application provides constructs comprising a single-domain antibody (sdAb) moiety that specifically recognizes cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Also provided are methods of making and using these constructs.

Abstract: A modified T cell comprises: i) an exogenous Negative Regulatory Factor (Nef) protein; and ii) a functional exogenous receptor comprising: (a) an extracellular ligand binding domain, (b) a transmembrane domain, and (c) an intracellular signaling domain (ISD) comprising a chimeric signaling domain (CMSD), wherein the CMSD comprises one or a plurality of Immune-receptor Tyrosine-based Activation Motifs (ITAMs), wherein the plurality of CMSD ITAMs are optionally connected by one or more linkers. Provided are also Nef proteins (e.g., non-naturally occurring Nef), and modified T cells comprising such Nef proteins. Provided are methods of making and uses thereof.

Abstract: Disclosed herein are multispecific, such as bispecific, antigen binding proteins comprising a first antigen binding domain comprising a heavy chain variable domain and a light chain variable domain, and a second antigen binding domain comprising a single-domain antibody. Pharmaceutical compositions comprising the multispecific antigen binding proteins, kits and methods of use thereof are further provided.

Abstract: The present invention relates to a human CD123-targeting chimeric receptor ligand, comprising an IL-3 molecule-based CD123 binding domain, a transmembrane region, and an intracellular signaling domain. The present invention provides a T cell modified by the human CD123-targeting chimeric receptor ligand and capable of specifically binding with CD123 on tumor cell surfaces, thereby having specific cytotoxicity on tumor cells. The present invention further relates to an application of the human CD123-targeting chimeric receptor ligand and an immune effector cell thereof in preparing an anti-tumor immunotherapy drug.