The present application provides constructs comprising an antibody moiety that specifically binds to PSMA (e.g., PSMA expressed on the surface of a cell). Also provided are methods of making and using these constructs.

A chimeric antigen receptor (CAR), including an antigen-binding domain, a CD8 or CD28 hinge domain, a DAP10 cytoplasmic domain, a 2B4 cytoplasmic domain, and a CD3z cytoplasmic domain, where the CAR is expressed in natural killer (NK) cells. A method for treating cancer, including administering a therapeutically effective amount of a composition containing a NK cell that expresses the CAR, or a therapeutically effective amount of a cellular therapeutic agent containing a NK cell that expresses the CAR, to a subject in need thereof.

The present disclosure describes a next-generation antisense transfer vector along with methods for a high titer lentivirus production, allowing efficient transduction of T cells with a constitutively expressed tumor-targeting receptor along with the activation-induced expression of various gene cargos. The disclosed antisense transfer vector and the methods can reduce virus production costs as well as enhance the efficacy and safety of next-generation CAR- or TCR-T cells reaching the clinic.

A fusion protein comprising: a first component comprising an antibody, or a fragment or variant thereof; and a second component comprising a cytokine trap or an adenosine deaminase or a fragment or variant thereof. In certain embodiments, the antibody is an anti-PD-1 antibody. In certain embodiments, the antibody binds to a tumor antigen, for example a MUC16 or MUC1 antigen. In certain embodiments, the cytokine trap is a TGF- trap. A polynucleotide encoding such a fusion protein and a vector comprising such a polynucleotide. A composition comprising the fusion protein. A method of using the composition, including in the treatment of cancer.

An aptamer-based switch technology is provided that enhances control of the use of chimeric antigen receptor (CAR)-related immunotherapies. The aptamer-based switch utilizes a synthetic bridge molecule containing a target-binding aptamer bound through a linker to a CAR-binding aptamer. A system containing a CAR and a corresponding aptameric bridge provides an immunotherapy platform that: (i) can be targeted to any desired antigen by choosing the target-binding aptamer of the bridge. (ii) can be redirected from one target to another by changing the target-binding aptamer: (iii) can be dosed according to the changing needs of an individual patient overtime by altering the administration protocol for the bridge: (iv) can be switched on or off quickly or gradually: (v) can be used as a companion diagnostic for a specific CAR therapy: (vi) can be integrated with either in vivo or ex vivo CAR expression: (vii) is non-immunogenic; and (viii) has low production costs.

Disclosed herein are cells that are immune cells or precursor cells thereof, which cells recombinantly express a chimeric antigen receptor (CAR), and a dominant negative form of an inhibitor of a cell-mediated immune response of the immune cell, wherein the CAR binds to a cancer antigen. Also disclosed herein are T cells that recognize and are sensitized to a cancer antigen, which T cells recombinantly express a dominant negative form of an inhibitor of a T cell-mediated immune response. Additionally provided are methods of using such cells to treat cancer in a subject in need thereof.

Described herein is a reliable method for preparing a potent vaccine useful for immunotherapy comprising the step of cryopreserving a population of cells undergoing immunogenic cell death, and using such cells to activate dendritic cells for use in immunotherapy. In a specific embodiment, the method comprises cryopreserving cancer cells undergoing cell death, which can be used to prepare a pharmaceutical composition for immunotherapy against cancer.

The present invention provides a chimeric cytokine receptor (CCR) comprising: (i) an exodomain which binds to a ligand selected from a tumour secreted factor, a chemokine and a cell-surface antigen; and (ii) a cytokine receptor endodomain.

An immune cell that is genetically engineered to express an exogenous alternative carbon source (ACS) metabolism gene, in which the ACS is not glucose and wherein the ability of the immune cell to metabolise the ACS is increased due to expression of the exogenous ACS metabolism gene. Also provided are polynucleotides, vectors, pharmaceutical compositions, methods of genetically engineering the immune cell and methods of use in therapy.

The present invention provides programmable universal cell receptors (PUCRs) comprising a catalytic antibody region, a transmembrane domain and a cytoplasmic domain. The PUCRs disclosed herein may be conjugated to a specificity agent in order to program the receptor for specificity to any molecule of interest. Also provided are nucleic acids encoding such PUCRs, and cells expressing the PUCRs. Such cells may be used in treating a variety of medical conditions and diseases including cancer and infectious diseases.