Disclosed herein are recombinant nucleic acids, comprising a 5 untranslated (5-UTR) sequence portion, a signal peptide sequence portion, a single chain antibody fragment sequence portion, a hinge region sequence portion, a transmembrane domain sequence portion, and one or more intracellular domain sequence portions. Also disclosed herein are modified natural killer (NK) cells comprising the recombinant nucleic acid described above. Further disclosed herein are methods of treating a tumor in a subject by administering the modified NK cells.

Disclosed herein are methods of generating therapeutic biomimetic nanovesicles (BioNVs) or therapeutic exosomes with lumen-loaded, therapeutically relevant biomolecules from hypoimmunogenic cells, compositions of therapeutic BioNVs or therapeutic exosomes, and methods of using the same for treatment or prevention of a disease or disorder.

The presently disclosed subject matter provides for antigen-recognizing receptors that specifically target B7-H3 and cells comprising such B7-H3-targeted antigen-recognizing receptors. The presently disclosed subject matter further provides uses of the B7-H3-targeted antigen-recognizing receptors for treatment.

The present disclosure is directed to leucine zipper-based sorting systems adapted to facilitate the expression and coordination of polypeptide sequences capable of improving the function of CAR T cells. The systems enable the generation of T cells engineered to express multiple combinations of CARs (multi-CAR), safety-switches, switch receptors, and/or cytokines.

In certain embodiments, this disclosure provides methods to generate DNA, RNA and/or DNA-peptide nanostructures based chimeric antigen receptor (CAR) T cell (engineered T cell) for cancer immunotherapy, and compositions made by these methods.

New synthetic expression cassettes comprising a minimal promoter and a cell-specific enhancer for expression of a nucleic acid of interest in one or more specific cell subtypes are disclosed. Vectors and host cells comprising such synthetic expression cassettes are also disclosed. The application also discloses methods for expressing a nucleic acid of interest, such as a nucleic acid encoding a chimeric antigen receptor (CAR), in a cell and for treating diseases or conditions such as cancers and genetic diseases using the synthetic expression cassettes, vectors and cells.

The present invention provides an endogenous signaling molecule activating chimeric antigen receptor (ESMA-CAR) comprising a) an antigen binding domain specific for an antigen, b) a first transmembrane domain, and c) an intracellular signaling domain comprising a co-stimulatory domain but no stimulatory domain, wherein said first transmembrane domain, when expressed on the cell surface of an immune cell, is able to recruit a stimulatory domain of an endogenous signaling molecule of said immune cell, wherein said endogenous signaling molecule is a protein comprising a second transmembrane domain and an intracellular signaling domain comprising a stimulatory domain, and wherein the interaction of the first transmembrane domain and the second transmembrane domain activates said immune cell upon binding of said antigen to said antigen binding domain of said ESMA-CAR. The present invention also discloses an immune cell expressing said ESMA-CAR and an in-vitro method for the generation of said ESMA-CAR.

The present invention is directed to a monoclonal mouse or humanized ROR1 antibody, or a single-chain variable fragment (scFv). The present invention is also directed to a mouse or humanized ROR1 chimeric antigen receptor (CAR) comprising from N-terminus to C-terminus: (i) a single-chain variable fragment (scFv) of the present invention, (ii) a transmembrane domain, (iii) at least one co-stimulatory domains, and (iv) an activating domain.

Provided herein are CD79b antibodies and CD79b-specific chimeric antigen receptors (CARs). Further provided herein are T cells expressing the CD79b-specific CARs and methods of treating cancer by administering the CD79b-specific CAR T cells.

The present disclosure relates to an engineered immune cell and use thereof. The present disclosure provides an engineered immune cell comprising a CAR or engineered TCR, which CAR or engineered TCR can comprise a first antigen binding domain and a second antigen binding domain. The engineered immune cells of the present disclosure, when administered into a subject, can inhibit the host immune cells such as T cells and/or NK cells and enhance the survival and persistence of the engineered immune cells in vivo, thereby exhibiting more effective tumor killing activity.