Herein, we provide genetically engineered immune effector cells, among other cells, which express CAR and secret a bispecific “trap” protein co-targeting a checkpoint protein and TGF-β or TGF-β receptor, so as to improve the antitumor immunity of the immune effector cells. Compared with conventional CAR-T cells and CAR-T cells secreting a polypeptide checkpoint inhibitor, the provided genetically engineered immune effector cells CAR-T cells with “trap” protein secretion attenuate inhibitory T cell signaling, enhance T cell persistence and expansion, and improve effector functionalities and resistance to exhaustion. In a xenograft mouse model, CAR-T cells with “trap” protein secretion significantly enhanced antitumor immunity and efficacy. Methods of using these genetically engineered cells, as well as using polynucleotides encoding the CAR and the “trap” protein, are also provided, for example, as a therapy against solid tumors.

The disclosure relates to an anti-TIM3 single-chain antibody. The amino acid sequence of the anti-TIM3 single-chain antibody is a sequence shown in SEQ ID NO. 1. T lymphocytes expressing the anti-TIM3 single-chain antibody can effectively kill tumor cells.

The present disclosure relates to compositions and methods for treating a subject having cancer associated with melanoma-associated antigen 4 (MAGE-A4) peptide. The disclosure includes the embodiments relate to a chimeric antigen receptor (CAR) that binds MAGE-A4 peptide, a polynucleotide encoding a CAR that binds the MAGE-A4 peptide, a modified cell comprising a CAR that binds the MAGE-A4 peptide, and a population of modified cells comprising a CAR that binds the MAGE-A4 peptide.

Provided a chimeric anti-drug antibody receptor (CADAR) specific for anti-drug-antibody-based B cell receptor (BCR), the anti-drug antibody is induced by a therapeutic anti-TNF-alpha monoclonal antibody. Also provided compositions comprising the CADAR, polynucleotides encoding the CADAR, vectors comprising a polynucleotide encoding the CADAR, engineered cells comprising the CADAR, and method using the same.

Provided are a technique for preparing universal humanised CAR19-DNT cells and an application therefor. Specifically provided are universal CAR-T cells targeting CD19, the universal CAR-T cells expressing an exogenous CAR construct, and the CAR construct having the structure shown in formula I: L-scFv-H-TM-C-CD3ζ (formula I); in the formula, L is nothing or a signal peptide sequence; scFv is an antibody single-chain fragment variable region sequence targeting CD19; H is nothing or a hinge area; TM is a transmembrane domain; C is a costimulatory signal molecule; and CD3ζ is a cytoplasmic signal conduction sequence derived from CD3ζ. The provided universal humanised CAR19-DNT cells have the advantages of low immunogenicity, not requiring gene editing to avoid GvHD, high safety, high specificity, and obvious tumour killing effects, and the provided construction method can be implemented in large-scale production, the production costs being low.

Provided by the present invention is a chimeric antigen receptor comprising a co-stimulatory receptor, the chimeric antigen receptor having a structure of scFv(X)-(Y)CD3zeta-2A-(Z); X comprises a tumor targeting antibody or a ligand or receptor capable of specifically binding to a tumor; Y is an intracellular region of the co-stimulatory receptor, and Z is a co-stimulatory receptor that is selected from among ICOS, CD28, CD27, HVEM, LIGHT, CD40L, 4-1BB, OX40, DR3, GITR, CD30, TIMI, SLAM, CD2, CD226. Further provided by the present invention are CAR-T cells that are constructed by means of a recombinant expression vector of the described chimeric antigen receptor, a preparation method therefor and an application thereof. The CAR-T cells described in the present invention significantly improve the tumor-killing abilities and amplification abilities thereof.

Provided herein are chimeric switch receptors (CSRs) comprising an ectodomain and/or transmembrane domain derived from an inhibitory receptor (e.g. PD1 or TGFβR2) fused to the transmembrane domain and/or intracellular signaling domain derived from one or more costimulatory proteins (e.g. CD2, CD28, MyD88, DAP10 or ICOS), or variants thereof. The chimeric switch receptors are designed to convert a signal e.g. an inhibitory signal such as an immunosuppressive signal in the form of PD-L1 or TGFβ into a costimulatory signal. Also provided are engineered immune cells engineered to functionally express a chimeric switch receptor and/or a CAR and optionally also a chimeric cytokine receptor (CCR), and populations thereof, methods of making and using the engineered cells, compositions and kits comprising them, and methods of treating e.g. cancer (e.g. solid or hematologic tumors) by administering the cells and the compositions.

Aspects of the present disclosure relate to compositions comprising a population of genetically engineered T cells that expresses a chimeric antigen receptor (CAR) that binds CD70, and methods of using such for the treatment of CD70+ solid tumors.

Provided are a humanized antibody specifically binding to EpCAM, and a chimeric antigen receptor, a nucleic acid, a vector, a cell, and the use associated with the humanized antibody. The humanized antibody comprises a heavy chain variable region and a light chain variable region. The sequence of the heavy chain variable region comprises a sequence shown in SEQ ID.1, a sequence shown in SEQ ID.2 and a sequence shown in SEQ ID.3. The sequence of the light chain variable region comprises a sequence shown in SEQ ID.4, a sequence shown in SEQ ID.5, and a sequence shown in SEQ ID.6. After the humanized antibody is constructed as a chimeric antigen receptor-T Cell, EpCAM-positive tumor cells can be specifically identified and killed, and tumors can be cleared in an animal body.

The present disclosure provides methods of producing a modified immune cell responsive to orthogonal cytokine signaling and a modified immune cell produced by said method. The present disclosure further provides a modified immune cell responsive to orthogonal cytokine signaling and methods for treating cancer comprising the modified immune cell.