The present disclosure provides methods and compositions for genetically modifying lymphocytes, for example T cells and/or NK cells. In some embodiments, the methods include reaction mixtures, and resulting cell formulations, that are created using whole blood, or a component thereof that is not a PBMC, and additionally comprise T cells and recombinant retroviral particles having polynucleotides that encode a CAR. In some embodiments, modified lymphocytes are reintroduced into a subject subcutaneously. In some embodiments, polynucleotides that provide T cells the ability to regulate cell survival and proliferation in response to binding to a CAR, are provided.

Chimeric antigen receptors containing CD123 antigen binding domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions, relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.

Provided herein are inhibitory chimeric antigen receptor compositions and cells comprising such compositions. Also provided are methods of using inhibitory chimeric antigen receptors and cells.

A method for coupling an antibody to a surface of a cell comprises the following steps: (1) chemically modifying sialic acid to obtain a sialic acid derivative containing an azide group; (2) absorbing the sialic acid derivative by the cell to obtain a cell modified with the azide group; (3) modifying the antibody with a conjunction compound to obtain a modified antibody; (4) co-culturing the modified antibody with the cell modified with the azide group. The present disclosure modifies natural sialic acid molecules in vitro through chemical synthesis methods, and utilizes modified natural sialic acid molecules to realize antibody modification on the surface of the cell. The modification method of the present disclosure is simple, low-cost, safe, and efficient, does not need complex gene editing or enzyme catalytic operation, and has universality. In theory, the modification method can realize the coupling of any antibody or macro-molecular substance on the surface of the cell.

The invention provides Natural Killer (NK) cells that have a reduced or ablated Signal Regulatory Protein Alpha (SIRPα-) function when compared to a NK cell having an unmodified SIRPα-function that effectively kills a population of cancer cells that express CD47.

Provided are a preparation method of trophoblasts with limited generations, a culture method of SNK cells and a method for treating tumor. The preparation method of trophoblasts includes the following steps: ligating a TAX2 gene to a lentiviral expression vector, followed by transferring into competent cells to obtain a lentivirus containing the TAX2 gene; infecting PBMCs with the lentivirus containing the TAX2 gene and culturing, and collecting CD3-cells; ligating a 41BBL-MICA fusion gene to the lentiviral expression vector, followed by transferring into the competent cells to obtain a lentivirus containing the 41BBL-MICA fusion gene; and mixing the CD3-cells with the lentivirus containing the 41BBL-MICA fusion gene and culturing to obtain the trophoblasts with limited generations.

This disclosure provides methods for producing multi-TCR T cells with enhanced anti-tumor phenotypes. The T cells are made from hematopoietic stem cells by introducing into the hematopoietic stem cells a first TCR and subsequently a second TCR.

The present invention provides a CD7 chimeric antigen receptor-modified NK-92MI cell and use thereof. In particular, the present invention provides an engineered NK cell expressing a chimeric antigen receptor (CAR), said CAR having an antigen-binding domain containing a nanobody VHH sequence targeting CD73. Said NK cell of the present invention can effectively kill tumor cells, especially T cell tumors, and has a good therapeutic effect on T cell leukemia (such as T-ALL).

Provided is a chimeric antigen receptor (CAR) specifically binding to CD138, an immune cell expressing same, and a pharmaceutical composition for the treatment or prevention of cancer including same as an active ingredient. It was confirmed that the CD138 chimeric antigen receptor (CAR)-expressing immune cell of the presently claimed subject matter efficiently exhibits strong cytotoxic ability against CD138-expressing (positive) cancer cells. Accordingly, it is expected that the CD138 chimeric antigen receptor (CAR)-expressing immune cell of the presently claimed subject matter can be utilized for the treatment of CD138-expressing (benign) cancer diseases.

Provided herein are pharmaceutical compositions, comprising a pharmaceutically acceptable carrier and therapeutically effective amounts of high affinity Natural Killer (haNK) cells and a therapeutic antibody in the form of a combined preparation. Also provided herein are methods for treating cancer by using the pharmaceutical composition comprising the haNK cells and the therapeutic antibody.