Abstract: Provided herein are binding molecules that each comprise (1) a Shiga toxin A subunit effector polypeptide and (2) a binding region capable of specifically binding CTLA-4 on the surface of cell, such as a tumor cell or an immunosuppressive immune cell. Further provided are methods of using such binding molecules to treat diseases and disorders, such as cancer.

Abstract: Provided herein are methods for treating or preventing cancer comprising administering to a subject in need thereof an effective amount of a HER2 binding molecule comprising a cytotoxic Shiga toxin A subunit effector polypeptide and a binding region capable of specifically binding an extracellular part of human HER2. The cancer may be a cancer that involves a cell which expresses or overexpresses HER2, such as a HER2-positive breast cancer, bile duct cancer, or a gastric or gastroesophageal adenocarcinoma.

Abstract: The present disclosure relates to PD-L1-binding molecules comprising a Shiga toxin effector region, a PD-L1-binding region, and a T cell epitope, and pharmaceutical compositions thereof. The PD-L1 binding molecules and pharmaceutical compositions thereof have uses for selectively killing specific cells (e.g., PD-L1 positive tumor cells and/or immune cells), for selectively delivering cargos to specific cells (e.g., PD-L1 positive tumor cells or immune cells), and as therapeutics for treating or slowing the progression of cancer (e.g., non-small cell lung cancer or squamous cell carcinoma of the head and neck). The present disclosure also relates to clinical methods for use of the disclosed PD-L1 binding molecules for treating a subject in need thereof.

Abstract: Provided herein are uses of CD20-binding molecules and one or more additional therapeutic agents. Certain CD20-binding molecules useful in the methods disclosed herein comprise 1) two or more CD20 binding regions and 2) one or more Shiga toxin effector polypeptides derived from an A Subunit of a member of the Shiga toxin family. Also disclosed herein are uses of CD20-binding molecules, and compositions thereof, (such as in conjunction with one or more additional therapeutic agents) for selective killing of specific cell types (such as a CD20-expressing tumor cell) and/or treating a variety of conditions, including cancers and tumors involving a CD20-expressing cell.