This document provides methods and materials related to self-masking tandem antibodies, for example, Self-Masking Anti-tumoR Tandem antibody (SMART-body). For instance, a self-masking tandem antibody may contain two antibody-based domains (each of which contains an antigen-binding site) that are connected by a linker peptide cleavable by a protease, and the connection between the two antibody-based domains results in the masking of at least one of the antigen-binding sites. In some embodiments, for example, the SMART-body is first provided as a single molecule which does not bind antigens because of the masking of the antigen-binding sites within the molecule, but subsequently, the linker peptide is cleaved by a protease expressed in a tumor microenvironment, severing the connection between and removing the masking of the two antibody-based domains, which can then bind antigens expressed in the tumor, achieving localized, targeted cancer therapy.