Fibronectin type III (FN3) domain antibodies, polynucleotides capable of encoding the FN3 domain antibodies or antigen-binding fragments, cells expressing FN3 domain antibodies or antigen-binding fragments, as well as associated vectors and detectably labeled FN3 domain antibodies or antigen-binding fragments may be used to engineer FN3 domain-targeting chimeric antigen receptors (CARs). Methods of making the FN3 domain antibodies, CARs, and engineered immune cells, and methods of using the engineered immune cells are applicable to treat diseases including cancer.