The present technology provides anti-Thyroid Stimulating Hormone Receptor (TSHR) multi-specific (e.g., bispecific) immunoglobulin-related compositions and methods of using the same to treat TSHR-associated pathologies including, but not limited to, thyroid cancers, T-ALL (T lineage acute lymphoblastic leukemia), multiple myeloma and Grave's disease. Kits for use in practicing the methods are also provided.

This document provides methods and materials involved in binding a binder (e.g., an antibody, antigen binding fragment, antibody domain, CAR, cell engager, and/or ADC) to a CD276 polypeptide. For example, binders (e.g., antibodies, antigen binding fragments, antibody domains, CARs, cell engagers, and/or ADCs) that bind to a CD276 polypeptide and methods and materials for using one or more such binding molecules to treat a mammal (e.g., a human) having cancer are provided.

Provided herein are methods and compositions for treating chordoma by preferentially targeting cancer stem cells than non-cancer stem cells in chordoma to effectively treat chordoma. In some embodiments, the chordoma tumors cells (preferentially the cancer stem cells in chordoma) are targeted by modified NK-92 cells (i.e., haNK cells) that express CARs that comprise means for binding to the PD-L1 and another tumor-specific antigen (e.g., EGFR). In some embodiments, the chordoma tumor cells are targeted by using NK cells in combination with a means for binding to means for binding to the PD-L1 and/or a means for binding another tumor antigen (e.g., EGFR). Each of the treatment methods disclosed above may be implemented prior to, and/or concurrent with radio- and/or chemotherapy, and/or may be employed with immune therapy as is discussed in more detail below.

Provided herein are immunomodulatory proteins comprising ICOSL variants and nucleic acids encoding such proteins. The immunomodulatory proteins provide therapeutic utility for a variety of immunological and oncological conditions. Compositions and methods for making and using such proteins are provided.

The invention features a method for treating graft versus host disease in a human, including administering to said human a therapeutically effective amount of a cell including a chimeric antigen receptor (CAR) which is specifically directed against an immune checkpoint molecule.

The current disclosure provides polypeptide constructs and cells comprising CDR3 regions of 9. 2 or both, that selectively bind a J-configuration of CD277 on a target cell. The disclosure also provides pharmaceutical compositions with the disclosed polypeptides or cells and methods of using these compositions in the treatment of cancer.