The present invention relates to a modified T cell, comprising (a) a disrupted endogenous CD28-encoding gene; and (b) a polynucleotide encoding a chimeric antigen receptor (CAR), wherein the CAR comprises in its ectodomain at least one antigen binding moiety that is capable of specific binding to the extracellular portion of CD28. The invention furthermore relates to a population of the modified T cells, to a method for generating modified T cells and medical and non-medical uses thereof.

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.

Compositions comprising and methods for the treatment of cancer using a NeoTCR based cell therapy with a modified TGF?RII expression.

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.

The present invention is inter alma concerned with a T cell receptor fusion construct comprising two specific peptidic moieties, one of these two moieties binding to the spike protein from coro-naviruses and binding to ACE2, in particular the spike proteins from SARS-CoV-2 and/or SARS-CoV-1, and one of these moieties being a protein of the T cell receptor complex. A vector comprising the genetic information encoding the T cell receptor fusion construct is also part of the present invention, as well as a process of transfecting or transducing T cells and a modified T cell comprising the T cell receptor fusion construct. Importantly, the present invention also relates to a T cell receptor fusion construct, a vector or a modified T cell for use in the treatment of a disease and in particular for use in the treatment of a disease caused by a coronavirus such as e.g. COVID-19 or SARS.

The present disclosure provides compositions and methods related to chimeric antigen receptors (CARs). In particular, the present disclosure provides CAR-based immunotherapeutic compositions that target tumor cells expressing glypican-3 (GPC3) for the treatment and prevention of cancer.

Chimeric antigen receptors containing tumor necrosis factor receptor superfamily member transmembrane 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.

The present disclosure provides, among other things, a method of cryopreserving and thawing cells that results in the thawed cells having high cellular viability and functionality post-thawing. In some embodiments, a large-scale method of cryopreserving cells is provided, the method comprising: (a) contacting the cells with a cryopreservation medium; (b) cooling the cells to 80 C. at a controlled rate to minimize latent heat of fusion; and (c) storing the cells in liquid nitrogen vapor phase, thereby cryopreserving the immune cells.

Provided are an anti-Claudin 18.2 antigen-binding fragment or antibody, and the use thereof. CDR3 of a heavy chain variable region of the antigen-binding fragment comprises an amino acid sequence shown in SEQ ID NO. 3. CDR3 of a light chain variable region of the antigen-binding fragment comprises an amino acid sequence shown in SEQ ID NO. 6. The provided antigen-binding fragment and anti-Claudin 18.2 antibody can specifically bind to a variety of sources of Claudin 18.2 proteins, have no binding effect on other proteins, and have a high specificity. In addition, a chimeric antigen receptor and a CAR-T cell prepared by means of the antibody have obvious cytotoxicity on cells stably expressing the Claudin 18.2 protein.

Antigen binding agents (e.g., single domain antibodies) that bind guanylyl cyclase C (GCC) and chimeric antigen receptors comprising GCC antigen binding domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions comprising these antigen binding agents and fragments thereof are also disclosed. The invention also provides therapeutic methods for utilizing the antibodies and antigen-binding molecules are provided herein.