The disclosure relates to immune cells comprising one or more vectors comprising a nucleic acid sequence encoding a chimeric antigen receptor specific for CD19 and a nucleic acid sequence encoding an enhancer of T cell priming (e.g., IL-18), compositions comprising the T cells, and methods of generating and/or using the T cells to treat diseases associated with the expression of CD19.

The present invention relates to a chimeric antigen receptor (CAR) comprising an extracellular domain that binds to one or more inflammation associated factor(s), a transmembrane/hinge domain and an intracellular domain. In a specific embodiment, a T regulatory (Treg) cell expressing a construct encoding said CAR which further comprising a Fox3p and a CAR activation-dependent NF-AT promoter that drives the expression of interleukin-10 and TGF-beta. It also relate to the methods of producing the CAR, the Treg cells expressing said CAR and the use of said CAR to treat autoimmune diseases such as transplant rejection, a graft versus host disease (GVHD) and cytokine release syndrome..

Embodiments of the disclosure include methods and compositions related to targeting of HLA-G-expressing cells with particular engineered receptors. In specific embodiments, NK cells are specifically engineered to bind HLA-G using particular chimeric antigen receptor constructs. In certain embodiments, vectors that express the HLA-G-targeting CARs also express particular a suicide gene and/or one or more particular cytokines.

Provided herein are T-cell receptor (TCR) fusion proteins (TFPs), T-cells engineered to express one or more TFPs, and methods of use thereof for the treatment of diseases, including cancer.

The invention features multi-specific fusion protein complexes with one domain comprising IL-15 or a functional variant and a binding domain specific to IL-12 or IL-18.

An immunoresponsive cell, such as a T-cell expressing (i) a second generation chimeric antigen receptor comprising: (a) a signalling region; (b) a co-stimulatory signalling region; (c) a transmembrane domain; and (d) a binding element that specifically interacts with a first epitope on a target antigen; and (ii) a chimeric costimulatory receptor comprising (e) a co-stimulatory signalling region which is different to that of (b); (f) a transmembrane domain; and (g) a binding element that specifically interacts with a second epitope on a target antigen.

This arrangement is referred to as parallel chimeric activating receptors (pCAR). Cells of this type are useful in therapy, and kits and methods for using them as well as methods for preparing them are described and claimed.

The present invention regards methods and/or compositions related to Natural Killer T cells that are engineered to harbor an expression construct that encodes IL-2, IL-4, IL-7, and/or IL-15 and additionally or alternatively comprise a chimeric antigen receptor (CAR). In specific embodiments, the CAR is a CAR that targets the GD2 antigen, for example in neuroblastoma

The present disclosure provides a composition comprising a nucleic acid delivery vehicle, a nucleic acid encoding interleukin-7 (IL-7), and a nucleic acid encoding chemokine (C-C motif) ligand 19 (CCL19), and its use thereof.

This invention relates to the field of therapeutics. Most specifically invention provides methods of generating in vitro engineered immune cells conditionally expressing interleukin-12 (IL-12) and one or more immunomodulators under the control of a gene expression modulation system in the presence of activating ligand and uses for therapeutic purposes in animals.

The disclosure provides methods of treating a malignancy comprising administering an effective dose of a chimeric receptor (e.g., CAR or TCR) genetically modified T cell immunotherapy. Some aspects of the disclosure relate to methods of determining an effective dose of a T cell immunotherapy comprising polyfunctional T cells prior to administration to the patient.