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.

Among the various aspects of the present disclosure is the provision of compositions and methods of making modified chimeric antigen receptor dendritic cells (CAR-DCs) and methods of use thereof. CAR-DCs can be used for the treatment of tumors and cancers, particularly solid tumors (as well as liquid tumors, blood cancer, and metastatic cancer).

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.

The present disclosure provides methods and compositions that include a polynucleotide that includes nucleic acids that encode an anti-idiotype polypeptide, as well as polypeptides that are encoded by the same, and cells that include and express the polypeptide. Disclosed methods include methods that utilize the anti-idiotype polypeptides as safety switches when they are used in combination with antibodies, include approved biologic antibodies, that include the recognized idiotype. Certain embodiments include anti-idiotype polypeptides and nucleotides encoding the same, that include an internal domain. This internal domain in some embodiments has functional domains that can induce proliferation or cell death upon binding of the anti-idiotype polypeptide by its target antibody.

The present invention relates to the optimization of a chimeric antigen receptor, in particular, the modification am intracellular co-stimulatory domain.

The present disclosure relates generally to the field of immuno-therapeutics, and particularly relates to novel chimeric polypeptides, e.g., chimeric antigen receptors (CARs) that include a transmembrane domain from CD28 and a hinge domain. In some cases, the hinge domain is capable of promoting dimerization of the CARs. The disclosure also provides compositions and methods useful for producing such molecules, as well as methods for the detection and treatment of health conditions, such as proliferative diseases (e.g., cancer).

The present disclosure provides anti-LILRB4 antibodies or antigen-binding fragments thereof, anti-LILRB4 chimeric antigen receptor protein, isolated polynucleotides encoding the same, pharmaceutical compositions comprising the same, and the uses thereof.