Abstract: The present disclosure relates to therapies for FOLR1 expressing cancers, such as pediatric acute myeloid leukemia, (e.g., CBF/GLIS acute myeloid leukemia), with antibody conjugates with binding specificity for folate receptor alpha (FOLR1) and its isoforms and homologs. Also provided are methods of using the combinations with antibody conjugates and compositions thereof, such as in therapeutic and palliative methods.

Abstract: Chimeric antigen receptors (CAR) that bind Preferentially Expressed Antigen in Melanoma (PRAME) ALY(SEQ ID NO: 94)/HLA-A2 are disclosed. The CAR can be used to treat PRAME/HLA-A2 expressing cancers such as the t(8;21), Inv(16), and KMT2A-r forms of acute myeloid leukemia (AML).

Abstract: 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.

Abstract: Some embodiments of the methods and compositions provided herein include chimeric antigen receptors (CAR)s which specifically bind to an epitope of CD33, such as an epitope encoded by exon 2 of CD33. Some embodiments include the use of such CARs for effective and safe therapies for myeloid leukemias, such as acute myeloid leukemia and chronic myeloid leukemia.

Abstract: Mesothelin (MSLN) is expressed on pancreatic cancers, ovarian cancers and mesotheliomas. The present disclosure provides antigen-binding molecules, including anti-MSLN antibodies, and bispecific antigen-binding molecules that bind to both MSLN and a T cell antigen (e.g., CD3) and activate T cells in the presence of MSLN-expressing tumor cells. The antigen-binding molecules of this disclosure are useful for the treatment of diseases and disorders in which a MSLN-targeted immune response is desired and/or therapeutically beneficial. For example, the antigen-binding molecules of the present disclosure are useful for the treatment of various cancers, including pancreatic cancer, ovarian cancer and mesotheliomas.