The present disclosure provides improved chimeric co-stimulatory receptors (CCRs), fusion proteins, genetically modified immune effector cells, and use of these compositions to treat disease.

Disclosed in the present application are CAR constructs that encode domains of anti-CD19 antibodies, T cells that include and express the CD19 CAR constructs, and methods of use, such as methods of treating disease, including hematological cancers, using CAR-T cells that express the CD19 CAR constructs.

Disclosed herein are chimeric antigen receptors (CARs) that target MUC1*. In some embodiments, the CARs have been optimized to reduce T cell exhaustion.

Disclosed herein are chimeric antigen receptors (CARs) that target MUC1*. In some embodiments, the CARs have been optimized to reduce T cell exhaustion.

The present invention relates to an ErbB2-specific NK-92 cell or cell line containing a lentiviral vector encoding a chimeric antigen receptor and preferably two vector integration loci in its cellular genome. The present invention further relates to the use of the ErbB2-specific NK-92 cell or cell line in the prevention and/or treatment of cancer, preferably ErhB2-expressing cancers. The present invention further relates to the use of the ErbB2-specific NK-92 cell or cell line as targeted cell therapeutic agent and/or for adoptive cancer immunotherapy. The present invention further relates to a method for generating an ErbB2-specific NK-92 cell or cell line as well as to a method for identifying au ErbB2-specific NK-92 cell or cell line and to the ErbB2-specific NK-92 cell or cell line obtained or identified by the methods as well as their uses.

A novel chimeric receptor composition, a recombinant vector, a cell, and an application thereof. The novel chimeric receptor composition includes a conventional chimeric antigen receptor (CAR), and a NKG2D chimeric receptor including a full-length sequence or a truncated fragment of NKG2D, DAP10, and/or DAP12, referred to as a SNR-armed CAR. The chimeric receptor composition enables a conventional CAR-T cell to express a NKG2D extracellular domain and an intracellular signal domain, expands a CAR-T antigen recognition spectrum, solves the tumor heterogeneity, achieves a lower level of cytokine release while enhancing the killing capability of CAR-T on tumor cells expressing target antigens, reduces the possibility of cytokine storm occurrence, and improves the CAR-T security.

Disclosed herein is an optimized CD99-targeting chimeric antigen receptor and application thereof, wherein a signal peptide, a single-chain antibody ScFv, strepII, a CD8 hinge, a CD28 transmembrane region, a CD28 intracellular domain, an intracellular co-stimulatory domain 4-1BB and CD3? chain are sequentially spliced in the chimeric antigen receptor is from the N-terminal to the C-terminal. The single-chain antibody ScFv can specifically recognize CD99 protein on the surface of tumor cells. The CD99-targeting chimeric antigen receptor is used to modify immune cells for the treatment of surface CD99-positive tumors.

In certain aspects, the disclosure relates to an immune cell that has been engineered to comprise one or more heterologous polynucleotides that promote thanotransmission by the immune cell. The immune cell may also comprise one or more nucleic acid sequences that encode a chimeric antigen receptor (CAR). Methods of promoting thanotransmission, promoting immune response, and treating cancer using the engineered immune cells are also disclosed.

Some embodiments of the methods and compositions provided herein include methods and/or systems for increasing an activity of a cell comprising a chimeric antigen receptor (CAR), comprising use of a first nucleic acid encoding a transcription response element (TRE); and a second nucleic acid encoding a CAR, wherein the activity of the cell is increased compared to a cell lacking the first nucleic acid. In some embodiments, the increased activity of the cell is selected from: (i) survival of a subject administered the cell, wherein the subject comprises a target cell comprising an antigen, wherein the CAR is capable of specifically binding to the antigen; (ii) killing of a target cell comprising an antigen, wherein the CAR is capable of specifically binding to the antigen; and (iii) proliferation of the cell in the presence of a target cell comprising an antigen, wherein the CAR is capable of specifically binding to the antigen.

The present invention relates to a new antibody or an antigen binding fragment thereof for use in the treatment of cancer by targeting a B cell malignancy, a chimeric antigen receptor comprising the same, and a use of the same. The antibody of the present invention is an antibody for specifically binding to CD19 that is highly expressed in cancer cells (particularly, blood cancer), has very low homology to a CDR sequence thereof compared to a CDR sequence of a conventional CD19 target antibody so that the sequence thereof is unique, and specifically binds to an epitope that is different from a FMC63 antibody fragment binding to CD19 of the conventional art. A cell expressing the chimeric antigen receptor comprising an anti-CD19 antibody or the antigen binding fragment of the present invention induces immune cell activity in response to a positive cell line expressing CD19, and thus may be utilized as a CAR-immune cell therapeutic agent.