In various embodiments, the present disclosure provides chimeric antigen receptors (CARs) which bind to mesothelin. The mesothelin CARs comprise an extracellular region comprising a binding domain that specifically binds to at least a portion of mesothelin, a transmembrane region, and an intracellular region comprising an effector domain or a portion or variant thereof and a costimulatory domain or a portion or variant thereof. Recombinant host cells expressing the mesothelin CARs are also provided, as well as compositions and methods of treatment, prevention, and manufacture comprising the same.

A CAR-immunocyte targeting an NKG2D ligand can be used in the preparation of a drug. The drug is used for: (i) removing the senescent cell, the NKG2D ligand in the senescent cell being up-regulated by 2-20 times, preferably 4-15 times, more preferably 10-20 times the normal cell; (ii) delaying individual senescence; and/or (iii) preventing and/or treating age-related diseases. The CAR-immunocyte targeting the NKG2D ligand is capable of specifically removing the senescent cell having high expression of the NKG2D ligand, and has higher in-vivo security.

An antigen-binding protein targeting CD70. In particular, the present invention relates to a chimeric antigen receptor containing the antigen binding protein and the use thereof, and cells containing or expressing the antigen binding protein. The antigen-binding protein binds to a CD70 protein at 1 nM of a K.sub.D value. The chimeric antigen receptor containing the antigen-binding protein has strong specific recognition and binding abilities to the CD70 protein. The cells containing or expressing the antigen-binding protein can secrete cytokines IL-2 and IFN-.

The present disclosure provides a chimeric antigen receptor (CAR) specific for albumin. 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.

Provided is a chimeric antigen receptor, comprising an antigen binding region, a transmembrane domain and an intracellular signaling region. The antigen binding region comprises an antibody specifically targeting CD7, and the intracellular signaling region consists of a co-stimulatory domain, a primary signal transduction domain, and a ?C chain or intracellular region thereof. Also provided are an engineered immune cell comprising the chimeric antigen receptor and a pharmaceutical composition thereof, and use of the engineered immune cell/pharmaceutical composition for treating cancers.

The present invention includes compositions and methods for treating AML utilizing bispecific CARs. In certain aspects, the invention includes a bispecific split CAR which binds CD13 and TIM-3 on AML cells. In one aspect, the invention provides a bispecific chimeric antigen receptor (CAR) comprising a first antigen binding domain capable of binding CD13, a first intracellular domain, a second antigen binding domain capable of binding TIM-3, a transmembrane domain, and a second intracellular domain.

Bi-specific chimeric antigen receptors (CARs) capable of binding to both CD19 and CD22 and immune cells expressing such. Also provided herein are therapeutic uses of such immune cells (e.g., CAR-T cells) for eliminating disease cells such as cancer cells.

Antibody-mediated rejection (ABMR) is one of the main obstacles to successful transplantation, including ABO blood group-incompatible (ABOi) transplantation. C4d deposition is a marker of ABMR and is also found in most ABOi allograft tissues. Described herein are anti-C4d CAR Tregs that suppress ABMR in ABOi allografts. Anti-C4d CAR Tregs prepared by retroviral transduction of CAR into CD62L +CD4 +CD25 +Tregs, expressed Foxp3, CD25, CTLA-4, LAP, and GITR to similar extents as non-transduced Tregs. Anti-C4d CAR Tregs were activated by specific binding to C4d and suppressed in vitro T cell proliferation as well as non-transduced Tregs. Furthermore, adoptive transfer of anti-C4d CAR Tregs significantly prolonged mouse ABOi heart allograft survival (P<0.05).

A family of chimeric antigen receptors (CARs) containing a CD123 specific scFv was developed to target different epitopes on CD123. In some embodiments, such a CD123 chimeric antigen receptor (CD123CAR) gene includes an anti-CD123 scFv region fused in frame to a modified IgG4 hinge region comprising an S228P substitution, an L235E substitution, and optionally an N297Q substitution; a costimulatory signaling domain; and a T cell receptor (TCR) zeta chain signaling domain. When expressed in healthy donor T cells (CD4/CD8), the CD123CARs redirect T cell specificity and mediated potent effector activity against CD123+ cell lines as well as primary AML patient samples. Further, T cells obtained from patients with active AML can be modified to express CD123CAR genes and are able to lyse autologous AML blasts in vitro. Finally, a single dose of 5.0?10.sup.6 CAR123 T cells results in significantly delayed leukemic progression in mice. These results suggest that CD123CAR-transduced T cells may be used as an immunotherapy for the treatment of high risk AML.

A method for producing CAR-M1 macrophages expressing a chimeric antigen receptor in vitro and in vivo includes using a conjugate of a non-viral gene delivery system and a chimeric antigen receptor gene. The CAR-M1 macrophages are produced in vivo by delivering genes encoding a chimeric antigen receptor and IFN-?, specifically to macrophages in the body, and thus does not require culturing and preparing an in-vitro cellular therapeutic agent, thus reducing the manufacturing costs of therapeutic agents. The CAR-M1 macrophages are a safer therapy since a non-viral vector is used, as compared to the production of CAR-M1 macrophages by gene delivery using a viral vector, and are a novel therapeutic candidate having the advantage of high anticancer efficiency for solid cancers, due to CAR-M1 macrophages in which intrinsic properties of macrophages infiltrating solid cancers and cancer cell phagocytosis are improved.