A combination cancer therapy comprising a small molecule drug conjugate (SMDC), which targets a cell-surface receptor on an immunosuppressive cell or a cancerous cell, and cytotoxic lymphocytes, which express a chimeric antigen receptor (CAR); and a method of treating a patient for cancer using the same.

Provided are compositions and methods for treating diseases associated with expression of mesothelin. Also provided are a chimeric antigen receptor (CAR) specific to mesothelin, vectors encoding the same, and recombinant T cells comprising the mesothelin CAR. Further provided are methods of administering a genetically modified T cell expressing a CAR that comprises a mesothelin binding domain.

The presently disclosed subject matter provides for methods and compositions for treating cancer (e.g., multiple myeloma). It relates to anti-CD56 antibodies, chimeric antigen receptors (CARs) that specifically target human CD56, and immunoresponsive cells comprising such CARs. The presently disclosed CD56-specific CARs have enhanced immune-activating properties, including anti-tumor activity.

The technology relates in part to binding molecules that specifically bind to a polypeptide that is the Isoform 2 of mesotheiin, or that specifically bind to an antigenic determinant (epitope) of the isoform 2 of mesotheiin, or that specifically bind to polypeptides containing an antigenic determinant (epitope) of the isoform 2 of mesotheiin, chimeric PD1 receptors that bind to PD ligands such as PDLs, to polynucleotides including vectors that encode such binding molecules, to ceils presenting such binding molecules and to methods of making such cells, to humanized forms of the binding molecules, and to methods of using such binding molecules, such as for treating cancers (e.g., ovarian cancers and mesotheliomas), including cancers in which the Isoform 2 of mesotheiin is specifically expressed and/or upregulated relative to normal tissues.

Provided is pharmaceutical composition for preventing or treating degenerative brain disease, containing regulatory T cells as an active ingredient. The pharmaceutical composition inhibits M1 microglial activation or transformation into DAM, promotes M2 polarization, inhibits tau protein phosphorylation, and increases the expression of anti-inflammatory cytokines, thereby protecting nerve cells, and thus it may be useful for the prevention or treatment of degenerative brain diseases.

Provided herein, in various embodiments, are mammalian cells (e.g., immune effector cells) comprising a nucleotide sequence encoding an exogenous fusogen. Also provided herein, in various embodiments, are methods of treating cancer in a subject in need thereof, comprising administering to the subject mammalian cells (e.g., immune effector cells) disclosed herein. Also provided herein, in various embodiments, are methods of killing a cancer cell, comprising contacting the cancer cell with mammalian cells (e.g., immune effector cells) disclosed herein.

The present invention relates to the field of therapeutic treatment, particularly of cell therapy based on CD16+ cells and NK (Natural Killer) cells. In particular, the invention relates to a pharmaceutical composition comprising a CD16+ cell, a NK cell or a NK cell precursor, in combination with a recombinant polypeptide comprising a modified Fc region, in particular a modified CH2 domain. More particularly, the invention relates to a composition comprising a CD16+ cell and/or a NK cell, in combination with a recombinant polypeptide capable of binding to the Fc?RIII (CD16) surface protein, wherein the recombinant polypeptide is non-covalently bound to the Fc?RIII (CD16) surface protein expressed by the CD16+ cell, and wherein said recombinant polypeptide comprises: (i) a modified CH2 domain of a wild-type human IgG1, bound, optionally through a linker, to (ii) a ligand binding domain, wherein the ligand binding domain comprises a sequence capable of binding to a target ligand; wherein the modified CH2 domain is characterized by comprising mutations S239D and I332E with respect to the CH2 domain of a wild-type human IgG1, and wherein said CH2 domain of a wild-type human IgG1 is represented by SEQ ID NO 1, and comprises sequence positions 231-340, according to the EU numbering.

The disclosure provides methods for the long-term expansion of granulocyte-macrophage progenitors, the granulocyte-macrophage progenitors generated therefrom, and uses of the granulocyte-macrophage progenitors thereof.

This disclosure describes chimeric antigen receptors for expression in a Natural Killer (NK) cell, pharmaceutical compositions that include NK cells (and/or iPSCs) modified to express a chimeric antigen receptor, and methods involving such chimeric antigen receptors. Generally, the chimeric antigen receptor includes an ectodomain that includes an antigen recognition region, a transmembrane domain linked to the ectodomain, and an endodomain linked to the transmembrane domain. The endodomain can include a signaling peptide that activates an NK cell.

The presently disclosed subject matter provides for methods and compositions for treating multiple myeloma. It relates to chimeric antigen receptors (CARs) that specifically target a G-protein coupled receptor (e.g., a G-protein coupled receptor family C group 5 member D (GPRC5D)), and immunoresponsive cells comprising such CARs. The presently disclosed CARs targeting a G-protein coupled receptor (e.g., GPRC5D) have enhanced immune-activating properties, including anti-tumor activity.