Sketch of a SMIP monomer consisting of four domains. The antigen binding site is on the left edge. scFv: modified single-chain variable fragment Fc: one half of a fragment crystallizable region VH: heavy chain variable domain VL: light chain variable domain CH2: constant domain 2 CH3: constant domain 3 (effector domain) Arrows: linker peptide (left) and hinge region (right) N: N-terminus C: C-terminus SMIPs are single-chain proteins that comprise one binding region, one hinge region as a connector, and one effector domain. The binding region is a modified single-chain variable fragment (scFv), and the rest of the protein can be constructed from the fragment crystallizable region (Fc) and the hinge region of an immunoglobulin G1 (IgG1). Genetically modified cells produce SMIPs as antibody-like dimers, which are about 30% smaller than real antibodies. Like ordinary monoclonal antibodies, SMIPs are monospecific, meaning they recognize and attach to a single antigen target to initiate their biological activity. SMIP drug candidates are intended to target antigens with the same specificity and predictable biological activity as monoclonal antibodies. Examples are TRU-015, a CD20 targeting SMIP under research for rheumatoid arthritis, and TRU-016, a CD37 targeting potential treatment for chronic lymphocytic leukemia and other B-cell cancers.
Small modular immunopharmaceutical
Small molecule drug conjugate
Pharmacological chaperone
Monoclonal antibody
Immunoconjugate
Generic drug
Prototype drug
Designer drug