The present invention relates to chimeric antigen receptors (CARs) specific to ICAM-1 comprising I domain of the .sub.L subunit of human lymphocyte function-associated antigen 1 (LFA-1). The invention particularly relates to CARs comprising human I domains having different affinities (1 mM to 1 nM Kd) to ICAM-1. CAR T cells comprising human I domain having a low affinity (1 to 200 M Kd) to ICAM-1 can avoid targeting healthy tissues with basal ICAM-1 expression while simultaneously exhibiting increased potency and long-term efficacy against tumor tissues with high ICAM-1 expression. The present invention also relates to an adoptive cell therapy method for treating cancer by administering the CAR-T cells comprising human I domain to a subject suffering from cancer, whereby the CAR T cells bind to the cancer cells overexpressing ICAM-1 and kill the cancer cells.

The present invention is directed to transduced T cells expressing at least 100,000 molecules of human somatostatin receptor 2 (SSTR2), which improves PET/CT imaging sensitivity. The present invention is also directed to transduced T cells expressing SSTR2 and chimeric antigen receptor (CAR). In one embodiment, the CAR is specific to human ICAM-1 and the CAR comprises a binding domain that is scFv of anti-human ICAM-1, or an I domain of the L subunit of human lymphocyte function-associated antigen-1. In another embodiment, the CAR is specific to human CD19, and the CAR comprises a binding domain that is scFv of anti-human CD19. The present invention is further directed to using the above transduced T cells for monitoring T cell distribution in a patient by PET/CT imaging and/or treating cancer.

The invention provides compositions and methods for treating diseases associated with expression of CD33. The invention also relates to chimeric antigen receptor (CAR) specific to CD33, vectors encoding the same, and recombinant T cells comprising the CD33 CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises a CD33 binding domain.

The present invention relates to a chimeric antigen-receptor (CAR) signalling system comprising; (i) a targeting component comprising an antigen-binding domain, a transmembrane domain and a first heterodimerization domain; and (ii) an intracellular signalling component comprising a signalling domain and a second heterodimerization domain; wherein spontaneous heterodimerization between the first and second heterodimerization domains causes the targeting component and signalling component to form a functional CAR complex.

The present invention provides combination therapies and methods of treating cancer, including, cancers that are resistant to PD-1 therapy. The combination therapies described herein comprise a DNA vaccine to a tumor antigen, anti-PD-1 therapy, and an anti-LAG-3 therapy, which provides an increased T cell response against the cancer.

The present invention provides a method of engineering a cell, comprising the steps of introducing into the cell: i) a site-directed nuclease which is capable of cleaving a target nucleotide sequence at the 3-end of Intron 1 of a Cytotoxic T-Lymphocyte Associated Protein 4 gene (CTLA4); and ii) a nucleic acid construct which comprises a nucleic acid sequence comprising one or more of exon 2, exon 3 and exon 4 of CTLA4, or a sequence with at least 70% identity to exon 2, exon 3 and/or exon 4 of the CTLA4 gene, and 5- and 3-homology arms, wherein each of the 5 and '3 homology arms is essentially complementary to a sequence flanking the target nucleotide sequence at the 3-end of Intron 1 of CTLA4.

The present invention provides an in-vitro method for the generation of a population of genetically modified natural killer (NK) cells comprising the steps in the following order: a) obtaining a sample comprising NK cells and other cells, b) enrichment of NK cells from said sample, c) introducing a genetic modifier 1 into said NK cells by electroporation, d) introducing a genetic modifier 2 into said NK cells by transduction, e) expanding said genetically modified NK cells, thereby generating a population of genetically modified NK cells.

The present invention is directed to genome editing systems, reagents and methods for immunooncology.

Provided is an antibody or an antigen-binding fragment thereof that binds to human TIGIT (T cell immunoreceptor with immunoglobulin and ITIM domains). Also provided are a nucleic acid molecule encoding the antibody or the antigen-binding fragment thereof, a vector and host cell containing the nucleic acid molecule, an immunoconjugate and composition comprising the antibody or the antigen-binding fragment thereof, and the use of the antibody or the antigen-binding fragment thereof in the preparation of a product for positively adjusting the activity of immune cells and/or improving the immune response, a product for reducing or eliminating the immunosuppressive effect of cells expressing TIGIT (such as Treg cells), and a kit for detecting the presence or absence of TIGIT and the level or activity of TIGIT.

Provided herein are compositions and methods for treating neuroendocrine cancer and preventing or treating metastasis originating from a neuroendocrine cancer.