A CAR-immunocyte targeting an NKG2D ligand can be used in the preparation of a drug. The drug is used for: (i) removing the senescent cell, the NKG2D ligand in the senescent cell being up-regulated by 2-20 times, preferably 4-15 times, more preferably 10-20 times the normal cell; (ii) delaying individual senescence; and/or (iii) preventing and/or treating age-related diseases. The CAR-immunocyte targeting the NKG2D ligand is capable of specifically removing the senescent cell having high expression of the NKG2D ligand, and has higher in-vivo security.

Compositions and methods for reducing HLA-A protein expression in a cell comprising genetically modifying HLA-A for use e.g., in adoptive cell transfer therapies.

The present invention provides genetically modified lymphocyte with reduced cytotoxicity. Also provided are methods of using these genetically modified lymphocytes to deliver cargo molecules to a target cell.

Chimeric antigen receptors (CAR) that bind Preferentially Expressed Antigen in Melanoma (PRAME) ALY(SEQ ID NO: 94)/HLA-A2 are disclosed. The CAR can be used to treat PRAME/HLA-A2 expressing cancers such as the t(8;21), Inv(16), and KMT2A-r forms of acute myeloid leukemia (AML).

The present invention relates to compositions, methods, uses and kits for combination therapies involving immunotherapies, such as adaptive cell therapy, e.g., T cell therapy, and an oncolytic virus (particularly parvovirus H-1), for treating subjects with cancer. The T cell therapy includes cells that express recombinant receptors such as chimeric antigen receptors (CARs). In some embodiments, the cancer is a solid tumor or a hematological malignancy.

Provided in the present disclosure are a KHL polypeptide, and the use thereof in the preparation of a TABP-EIC cell. In addition, also provided in the present disclosure are a KHL polypeptide conjugate, a tumor-antigen-binding polypeptide containing the KHL polypeptide, a DNA molecule, a carrier, a host cell and a pharmaceutical composition. The tumor-antigen-binding polypeptide is composed of the KHL polypeptide, a transmembrane domain and/or a signal transduction domain.

The invention provides a modified T cell, or an isolated population of immune cells expressing a CXCR3 isoform selected from CXCR3A, CXCR3B, and CXCR3alt, and optionally, further expressing transgenes comprising an artificial T cell receptor, and/or a CXCR3 ligand, for use as a medicament. The invention also provides the methods to obtain said cells, or populations of cells from a plurality of immune cells derived from a human subject. The invention also relates to assessment of CXCR3 splice variants and its ligands CXCL9, CXCL10, and CXCL11 in muscle-invasive bladder cancer (MIBC) patients, to enable patients to be stratified for their predicted response to a chemotherapy drug treatment, or clinical outcome.

A method for producing CAR-M1 macrophages expressing a chimeric antigen receptor in vitro and in vivo includes using a conjugate of a non-viral gene delivery system and a chimeric antigen receptor gene. The CAR-M1 macrophages are produced in vivo by delivering genes encoding a chimeric antigen receptor and IFN-?, specifically to macrophages in the body, and thus does not require culturing and preparing an in-vitro cellular therapeutic agent, thus reducing the manufacturing costs of therapeutic agents. The CAR-M1 macrophages are a safer therapy since a non-viral vector is used, as compared to the production of CAR-M1 macrophages by gene delivery using a viral vector, and are a novel therapeutic candidate having the advantage of high anticancer efficiency for solid cancers, due to CAR-M1 macrophages in which intrinsic properties of macrophages infiltrating solid cancers and cancer cell phagocytosis are improved.

Disclosed are CAR polypeptides comprising a target specific receptor and a death domain. Disclosed are CAR polypeptides comprising a LINGO1 antigen binding domain, a transmembrane domain, and an intracellular signaling domain. Disclosed are CAR cells comprising one or more of the disclosed CAR polypeptides. Disclosed are cells comprising an altered ?4?1 integrin. Disclosed are methods of treating comprising administering one or more of the disclosed cells to a subject in need thereof.

Activity-inducible fusion proteins whose activity is post-translationally regulated utilizing a hsp90 binding domain and a drug molecule are described. In the absence of the drug molecule, the activity-inducible fusion proteins are inactivated but can be activated by a relevant physiological parameter in the presence of the drug molecule. Examples of the activity-inducible fusion proteins include chimeric antigen receptors (CAR) wherein the relevant physiological parameter is antigen binding.