Targeted therapeutics for the treatment of cancers expressing FOLR1, MEGF10, HPSE2, KLRF2, PCDH19, and/or FRAS1 are described. The targeted therapeutics can include a chimeric antigen receptor (CAR) expressed by an immune cell or an antibody-targeted therapeutic. The targeted therapeutics can be used to treat a variety of cancers including solid tumors and blood cancers, such as CBFA2T3-GLIS2 acute myeloid leukemia (C/G AML).

The present invention provides a chimeric antigen receptor (CAR) comprising a CD21-binding domain, a transmembrane domain and an intracellular domain.

Disclosed herein are cells that are immune cells or precursor cells thereof, which cells recombinantly express a chimeric antigen receptor (CAR), and a dominant negative form of an inhibitor of a cell-mediated immune response of the immune cell, wherein the CAR binds to a cancer antigen. Also disclosed herein are T cells that recognize and are sensitized to a cancer antigen, which T cells recombinantly express a dominant negative form of an inhibitor of a T cell-mediated immune response. Additionally provided are methods of using such cells to treat cancer in a subject in need thereof.

Provided herein are antibodies and antigen binding fragments thereof specific for endomucin (EMCN). Also provided herein are cells, nucleic acids, vectors, compositions, and methods directed to antibodies or antigen-binding domains thereof specific for EMCN.

Provided herein are compositions and methods for providing long-term and sustained CAR T cell efficacy. For example, expression cassettes that encode both a GPC2-targeting chimeric antigen receptor and a bispecific innate immune cell engager binding both GD2 on tumor cells and CD16A on natural killers (NK) and macrophages are provided. In addition, T cells that both expression a GPC2-targeting chimeric antigen receptor on their surface and secrete a bispecific innate immune cell engager binding both GD2 on tumor cells and CD16A on natural killers (NK) and macrophages are provided.

Provided herein are recombinant antigen receptors, for example chimeric antigen receptors (CARs), that comprise modified cytoplasmic domains that provide improved signalling and thereby provide improved performance and safety. Also provided are polynucleotides encoding the recombinant antigen receptors, vectors comprising the polynucleotides, and engineered immune cells comprising the vectors and/or polynucleotides. The invention further provides methods for engineering immune cells to express the recombinant antigen receptors. Improved recombinant antigen receptor signalling is also provided by co-expressing a first recombinant antigen receptor and a second recombinant antigen receptor or co-expressing a recombinant antigen receptor and a protein involved in transducing the signal from the activated recombinant antigen receptor. Also provided are methods of treating a variety of conditions, including, but not limited to, blood cancers and cancers characterized by solid tumors, by administering the engineered cells to patients suffering from such a condition.

The present invention provides methods for detecting CEACAM1 expression in a cancer patient. In particular, methods according to the present invention include contacting a biological sample having Tumor Infiltrating Lymphocytes expressing CEACAM1 with an anti-CEACAM1 antibody labeled with a detectable moiety.

The invention provides compositions and methods for treating ovarian cancer. Specifically, the invention relates to administering a genetically modified T cell having -folate receptor (FR) binding domain and CD27 costimulatory domain to treat ovarian cancer. In an embodiment, the FR binding domain is fully human, thereby preventing a host immune response.

This disclosure provides, for instance subset-optimized CART cells and related methods. For instance, the disclosure describes methods and compositions of CD4 and CD8 T cells that express CARs containing specific combinations of intracellular signaling domains can be used to increase persistence and anti-tumor activity of the infused CAR-expressing T cells for treating a subject having a disease, e.g., a cancer.

Modified cells comprising a transmembrane polypeptide comprising at least one extracellular target receptor-binding domain, a transmembrane domain and an intracellular domain, wherein said intracellular domain is not capable of transducing any signal are provided. Methods of inducing or inhibiting signaling by a target receptor in a target cell comprising contacting the target cell with a modified cell of the invention are also provided.