In one embodiment, the present disclosure provides an engineered cell having a first chimeric antigen receptor polypeptide including a first antigen recognition domain, a first signal peptide, a first hinge region, a first transmembrane domain, a first co-stimulatory domain, and a first signaling domain; and a second chimeric antigen receptor polypeptide including a second antigen recognition domain, a second signal peptide, a second hinge region, a second transmembrane domain, a second co-stimulatory domain, and a second signaling domain; wherein the first antigen recognition domain is different than the second antigen recognition domain.

Provided are modified cells and methods for their use in treating cancer. The cells are modified to express and secrete a Bi-specific T cell engager (BiTE) that includes a segment that specifically binds to human Folate Receptor alpha (FR) and a segment that that specifically binds to human CD3, such as CD3e. The modified cells can be T cells. Methods for producing the modified cells are also provided.

The invention features a method for treating graft versus host disease in a human, including administering to said human a therapeutically effective amount of a cell including a chimeric antigen receptor (CAR) which is specifically directed against an immune checkpoint molecule.

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 provides new anti-cancer immune cells engineered to express chimeric receptors which, unlike the conventional chimeric antigen receptors (CAR), employ the extracellular domain of PD-1 that is capable of binding PD-L1 that is expressed on a target tumor cell. The immune cell is preferably an immature myeloid cell that is p50 deficient. Such an engineered immune cell exhibits improved therapeutic efficacy as compared to the conventional immune cell therapies and is more broadly applicable to different types of cancers expressing, or induced to express PD-L1.

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.

The present disclosure provides compositions and methods for targeting SOX2 antigen to, for example, treat or manage cancer. Provided compositions include binding proteins that are capable of binding to a SOX2 antigen:HLA complex. Also provided are polynucleotides and transgene constructs encoding binding proteins, such as a T cell receptor or a chimeric antigen receptor, that specifically bind to a SOX2 antigen. Such polynucleotides and transgene constructs can be introduced into an immune cell, such as a T cell, and used in immunotherapy in a subject having or at risk for a cancer associated with SOX2 expression or activity. The present disclosure also provides immunogenic compositions comprising SOX2 antigens, and related uses.

Provided are methods and compositions for obtaining functionally enhanced derivative effector cells obtained from directed differentiation of genomically engineered iPSCs. Also provided are derivative cells having stable and functional genome editing that delivers improved or enhanced therapeutic effects. Also provided are therapeutic compositions and the use thereof comprising the functionally enhanced derivative effector cells alone, or with antibodies or checkpoint inhibitors in combination therapies.

The current disclosure provides polypeptide constructs and cells comprising CDR3 regions of 9. 2 or both, that selectively bind a J-configuration of CD277 on a target cell. The disclosure also provides pharmaceutical compositions with the disclosed polypeptides or cells and methods of using these compositions in the treatment of cancer.

Provided are a fusion protein of an anti-TIGIT antibody and IL2 or a variant thereof, and an application thereof. Specifically, a fusion protein is provided, which comprises: (a) a first polypeptide comprising an anti-TIGIT antibody or an antigen-binding fragment thereof; and (b) a second polypeptide comprising interleukin-2 (IL-2) or a variant thereof having a lymphocyte growth promoting activity, the second polypeptide being fused to the first polypeptide. Also provided are an application of such a fusion protein in positively regulating immune cell activity and/or improving immune responses; and/or, an application thereof in the treatment of cancer, immunodeficiency or inflammatory diseases, or infectious diseases.