Disclosed herein are anti-mesothelin antibodies and antigen-binding fragments, chimeric antigen receptors (CARs) having these anti-mesothelin antibodies and antigen-binding fragments (mesothelin CARs) and genetically modified immune effector cells having such mesothelin CARs. Polynucleotides encoding the anti-mesothelin antibodies and antigen-binding fragments and mesothelin CARs are also provided herein. Compositions comprising anti-mesothelin antibodies and antigen-binding fragments and mesothelin CARs are also provided herein. The present disclosure also relates to uses of the anti-mesothelin antibodies and antigen-binding fragments and genetically modified immune effector cells having such mesothelin CARs in cancer treatment.

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.

The present invention provides compositions and methods for treating cancer in a human. The invention includes relates to administering a genetically modified T cell expressing a CAR having an antigen binding domain, a transmembrane domain, a CD2 signaling domain, and a CD3 zeta signaling domain. The invention also includes incorporating CD2 into the CAR to alter the cytokine production of CAR-T cells in both negative and positive directions.

Disclosed herein are methods for culturing CAR-modified immune cells with at least one Retinoic Acid Receptor and/or Retinoid X Receptor active agent.

Disclosed herein are methods for culturing CAR-modified immune cells with at least one Retinoic Acid Receptor and/or Retinoid X Receptor active agent.

The present invention provides compositions and methods for treating cancer in a human. The invention includes relates to administering a genetically modified T cell expressing a CAR having an antigen binding domain, a transmembrane domain, a CD2 signaling domain, and a CD3 zeta signaling domain. The invention also includes incorporating CD2 into the CAR to alter the cytokine production of CAR-T cells in both negative and positive directions.

Disclosed herein are methods for treating cancer comprising administering CAR-modified immune cells and at least one Retinoic Acid Receptor agonist.

Disclosed herein are methods for treating cancer comprising administering CAR-modified immune cells and at least one Retinoic Acid Receptor agonist.

Disclosed herein are methods for treating cancer comprising administering CAR-modified immune cells and at least one Retinoic Acid Receptor and/or Retinoid X Receptor active agent.

Disclosed herein are methods for treating cancer comprising administering CAR-modified immune cells and at least one Retinoic Acid Receptor and/or Retinoid X Receptor active agent.