Hematopoietic stem/progenitor cells (HSPC) and/or non-T effector cells are genetically modified to express (i) an extracellular component including a ligand binding domain that binds a cellular marker preferentially expressed on an unwanted cell; and (ii) an intracellular component comprising an effector domain. Among other uses, the modified cells can be administered to patients to target unwanted cancer cells without the need for immunological matching before administration.

Novel therapeutic immunotherapy compositions comprising at least two vectors, each vector encoding a functional CAR, whereby the combination of vectors results in the expression of two or more non-identical binding domains, wherein each vector encoded binding domain(s) are covalently linked to a transmembrane domain and one or more non-identical intracellular signaling motifs are provided herein as well as are methods of use of same in a patient-specific immunotherapy that can be used to treat cancers and other diseases and conditions.

The present disclosure provides modified immune cell (e.g., modified T cell) comprising an exogenous T cell receptor (TCR) having specificity for NY-ESO-1. The present disclosure provides modified immune cells or precursors thereof (e.g., modified T cells) comprising an exogenous TCR and a switch receptor. Gene edited modified cells are also provided, such that the expression of one or more of an endogenous T-cell receptor gene (e.g., TRAC, TRBC) or an endogenous immune checkpoint gene (e.g. PD-1 or TIM-3) is downregulated.

The present disclosure concerns dosages for the treatment of human patients susceptible to or diagnosed with a disease, such as cancer. Provided are methods for administering chimeric antigen receptor (CAR)-T cells. Also provided are compositions and articles of manufacture for use in the methods.

A chimeric antigen receptor, includes an extracellular domain, a transmembrane domain, and an intracellular domain, which are connected in sequence, where the extracellular domain includes an antigen recognition region and a hinge region, and one end of the intracellular domain which is connected to the transmembrane domain is connected to a CD3 intracellular region. The chimeric antigen receptor can further improve the treatment effect of B-cell leukemia lymphoma, and reduce inflammatory cytokines generated from macrophage mononuclear cell activation by down-regulating cytokines, so that cytokine storm can be prevented in an early stage, and the risk of neurotoxicity can be reduced. The treatment effect of mesothelin high-expression solid tumors is further improved in mesothelin-positive tumor treatment, and the prevention of cytokine storm and the reduced risk of neurotoxicity can be realized at an early stage.

Circular RNA, along with related compositions and methods are described herein. In some embodiments, the inventive circular RNA comprises group I intron fragments, spacers, an IRES, duplex forming regions, and an expression sequence. In some embodiments, the expression sequence encodes an antigen. In some embodiments, circular RNA of the invention has improved expression, functional stability, immunogenicity, ease of manufacturing, and/or half-life when compared to linear RNA. In some embodiments, inventive methods and constructs result in improved circularization efficiency, splicing efficiency, and/or purity when compared to existing RNA circularization approaches.

The present disclosure provides a chimeric antigen receptor (CAR) for activating dendritic cells (DCs) in an immunosuppressive tumor environment. The present disclosure also provides compositions comprising the CAR, polynucleotides encoding the CAR, vectors comprising a polynucleotide encoding the CAR, engineered cells comprising the CAR, and method using the same.

The invention relates to an improved system for generating immunotherapeutic T-cells comprising a chimeric antigen receptor (CAR).

This invention provides, as a therapeutic method for eradication of neoplastic diseases of the blood with poor diagnosis, a cell co-expressing a chimeric antigen receptor (CAR) protein and a CXCL12 receptor protein on the cell membrane, and an agent and a pharmaceutical composition having anti-tumor activity, which comprises such cell.

Anti-CD19 antibodies (e.g., UniAbs?) and CAR-T structures are disclosed, along with methods of making such antibodies and CAR-T structures, compositions, including pharmaceutical compositions, comprising such antibodies and CAR-T structures, and their use to treat disorders that are characterized by the expression of CD19.