The present disclosure provides bispecific chimeric antigen receptors targeting CD20 and BCMA. The CAR may comprise an scFv targeting CD20 and an scFv targeting BCMA, a hinge region, a transmembrane domain, a co-stimulatory region, and a cytoplasmic signaling domain. The chimeric antigen receptors can be used to treat autoimmune disorders or cancer.

Provided herein are antibodies and antigen-binding portions thereof that bind to tumor endothelial marker 1 (TEM1), as well as methods of using the disclosed antibodies and antigen-binding portions thereof, including methods of treating cancer, reducing tumor growth, reducing tumor metastasis, and/or reducing tumor-associated fibrosis in a subject in need thereof.

Disclosed herein are methods of gene editing, or endogenous suppression, of cytokines/chemokines/transcription factors secreted from chimeric antigen receptor (CAR)-bearing immune effector cell such as CAR-T cells for the mitigation of cytokine release syndrome and/or CAR-T associated neuropathy. These methods involve insertion of the CAR into a locus of a cytokine gene, blocking its expression. Also disclosed herein are (CAR)-bearing immune effector cells with CARs inserted into a locus of a cytokine gene, and methods of treatment of diseases with immunotherapy with a reduced incidence of cytokine release syndrome and/or CAR-T associated neuropathy.

Provided herein, in some embodiments, are methods and compositions (e.g., cell compositions) for the treatment of cancer, such as LIV1.sup.+ malignancies.

Provided are systems for modifying a cell. Also provided are methods for using the systems for modifying a cell.

Provided are a disialoganglioside 2 (GD2) chimeric antigen receptor (CAR) and use thereof. A humanized GD2 single-chain variable fragment (scFv) antibody has activity of binding to a GD2 antigen, where the humanized GD2 scFv has a more than 80% of amino acid sequence identity with SEQ ID NO. 1. Further provided are the GD2 CAR and a chimeric antigen receptor T (CAR-T) cell expressing the GD2 CAR. The humanized GD2 scFv has better bioactivity and compatibility. Binding the GD2 CAR to GD2 has a better response effect, a stronger immune response and a better long-term effect. The CAR-T cell has higher safety and persistence and an extremely high application value.

Disclosed are an antibody or an antigen binding fragment or chimeric antigen receptor thereof which binds to Claudin18.2, and a preparation method and a use. The chimeric antigen receptor sequentially comprises the antibody or the antigen binding fragment thereof which binds to the Claudin18.2 antigen, an extracellular hinge region, a transmembrane region and an intracellular signaling region. The antibody or the antigen binding fragment or chimeric antigen receptor thereof has stronger affinity and killing capability for cells secreting Claudin18.2, and a better tumor inhibiting effects.

The present disclosure relates to methods of treating a patient with a cancer by administering to the patient a composition comprising CAR T cells and a small molecule linked to a targeting moiety by a linker. The disclosure also relates to compositions for use in such methods.

Provided is a cell, comprising and/or expressing a chimeric antigen receptor targeting claudin 18.2 (CLDN18.2), and a chimeric antigen receptor targeting mesothelin (MSLN) protein. Also provided is an expression vector, comprising a nucleic acid sequence which encodes the chimeric antigen receptor targeting CLDN18.2 and a nucleic acid sequence which encodes the chimeric antigen receptor targeting MSLN. Also provided are a preparation method for and a use of the cell and/or the expression vector.

Disclosed herein are antibodies or antigen binding fragments that specifically bind human GPRC5D. Also disclosed are chimeric antigen receptors and chimeric antigen receptor transgenes comprising an antigen binding domain that specifically binds human GPRC5D and fusion proteins comprising a Henipavirus glycoprotein G and a GPRC5D antibody, or an antigen binding fragment thereof. Viral vectors and other compositions containing the antibodies or antigen binding fragments thereof, chimeric antigen receptors and chimeric antigen receptor transgenes, and fusion proteins are disclosed. The present disclosure additionally relates to cells expressing chimeric antigen receptors, as well as methods of delivering the various antibodies and chimeric antigen receptors and methods of using cells expressing the chimeric antigen receptors.