The present invention relates to a fusion protein and the use thereof. The fusion protein includes, from N to C terminals, a first moiety, an Fc segment, a linking moiety comprising a moiety selected from a linker and a protein or polypeptide selected from IL2 or scFv, and a substrate moiety of transpeptidase A; the linker includes a sequence selected from the group consisting of (1) (GGGGS)n, wherein when the linking moiety includes the protein or polypeptide and the linker, n≥1; when the linking moiety only includes the linker, n≥3; and (2) (EAAAK)n, n≥1; the substrate moiety includes LPXTG. The fusion protein can be directly connected to cells to enable the cells to have a targeting property, is more simple than an existing method for preparing targeting cells by means of cell transfection, and can also reduce the risk possibly generated by an effector cell genome operation.

A composition containing, as an active ingredient, a nucleic acid molecule that inhibits expression of type II HLA protein and uses thereof are disclosed. The composition is useful for inhibiting immunogenicity of mammalian cells. A method of producing hypoimmunogenic mammalian cells using the composition is also disclosed. The cells which are allogeneic transplanted for disease treatment, such as stem cells or immune cells, may be used as an effective cell therapy product having a long-term activity with minimized immune rejection in the recipient's body.

Provided herein are a recombinant chimeric antigen receptor (CAR) fusion protein, a method of modifying an immune cell into a CAR immune cell by treating the immune cell with the recombinant CAR fusion protein, and a method of treating cancer by administering the CAR immune cell to a subject in need thereof.

Provided are therapeutic agent including nucleic acid and CAR-modified immune cell and the use thereof. The therapeutic agent comprises first composition and second composition, the first composition comprises a nucleic acid having a labeling polypeptide coding sequence for being introduced into a tumor cell and/or a cancer cell; the labeling polypeptide has an extracellular antigen determining region, a spacer portion, and a transmembrane portion that are operatively linked, which can be expressed to form modification on the surface of the tumor cell and/or cancer cell; the extracellular antigen determining region comprises one or more epitope polypeptides; wherein, amino acid sequences of proteins on cell membrane or secreted proteins of mammal do not comprise the epitope polypeptide amino acid sequence in the natural state; the second composition comprises chimeric antigen receptor modified immune cell which specifically recognize and bind to the extracellular antigen determining region. The therapeutic agent achieves synergistic therapeutic effect.

Genetically modified cells, including a recombinant nucleic acid expression construct including a first nucleic acid sequence region encoding a chimeric antigen receptor (CAR) that includes an extracellular antigen-binding domain recognizing a carcinoembryonic antigen (CEA) protein, a second nucleic acid sequence region encoding a checkpoint inhibitory molecule, and a third nucleic acid sequence region encoding an immune stimulatory cytokine. In some aspects, the genetically modified cells are T cells or NK cells, preferably cytotoxic T lymphocytes. Anti-CEA CAR-T cells or anti-CEA CAR-NK cells preferentially recognize a membrane-bound CEA protein and express a checkpoint inhibitory molecule and/or an immune stimulatory interleukin in proximity to tumor tissue. Medical use of the cells may relate to treatment of a medical disorder associated with the presence of pathogenic cells expressing CEA, preferably cancer cells, more preferably cancer cells of solid malignancies.

The present disclosure provides hybrid promoter sequences comprising an MND promoter and HTLV enhancer capable of driving high levels of sustained expression of a heterologous sequence in immune cells, particularly Natural Killer (NK) cells. The disclosure also provides compositions comprising such vectors, immune cells which have been genetically modified to contain the vectors, as well as methods of using the same for inducing immune responses and treating cancer and other conditions.

Methods, compositions and kits for enhancing cell mediated killing of cancer cells are provided. Methods to enhance killing of such cancers, e.g. pAML, comprise administering an effective dose of a CD200 blocking agent in combination with an effective dose of cytotoxic immune cells.

Described herein are immune cells comprising: a T-cell receptor (TCR) and a chimeric stimulating receptor (CSR) that comprises (i) a ligand-binding module that is capable of binding or interacting with a target ligand; (ii) a transmembrane domain; and (iii) a CD30 costimulatory domain, in which the CSR in the immune cells lacks a functional primary signaling domain. Also provided herein are methods of using the same or components thereof (e.g., the CSR) for therapeutic treatment of cancers (e.g., solid tumor cancers).

Provided herein are populations of placental-derived natural killer cells comprising a cleavage resistant CD16. Also provided are methods of treating diseases, disorders or conditions in a human subject comprising administering to the subject an effective amount of a population of placental-derived natural killer cells comprising a cleavage resistant CD16 to the subject so as thereby to provide an effective treatment of the to the subject. The cells, such as CYNK cells, can be placental CD34+ cell-derived natural killer (NK) cells. The diseases, disorders or conditions include cancers such as multiple myeloma and lymphoma. The present invention also provides compositions comprising populations of placental-derived natural killer cells comprising a cleavage resistant CD16 for the treatment of a subject and methods of their use.

The presently disclosed subject matter provides chimeric antigen receptors (CARs) that specifically target CD19 and cells comprising such CD19-targeted CARs. The presently disclosed subject matter further provides uses of the CD19-targeted CARs for treatment, e.g., for treating blood cancer.