Abstract: Antigen binding agents (e.g., single domain antibodies) that bind guanylyl cyclase C (GCC) and chimeric antigen receptors comprising GCC antigen binding domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions comprising these antigen binding agents and fragments thereof are also disclosed. The invention also provides therapeutic methods for utilizing the antibodies and antigen-binding molecules are provided herein.