Small modular immunopharmaceuticals, or SMIPs for short, are artificial

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

s that are intended for use as

pharmaceutical drug A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field an ...

s. They are largely built from parts of antibodies (immunoglobulins), and like them have a

binding site In biochemistry and molecular biology, a binding site is a region on a macromolecule such as a protein that binds to another molecule with specificity. The binding partner of the macromolecule is often referred to as a ligand. Ligands may includ ...

for

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respons ...

s that could be used for

monoclonal antibody therapy Monoclonal antibody therapy is a form of immunotherapy that uses monoclonal antibodies (mAbs) to bind monospecifically to certain cells or proteins. The objective is that this treatment will stimulate the patient's immune system to attack those ...

. SMIPs have similar biological half-life and, being smaller than antibodies, are reasoned to have better tissue penetration properties. They were invented by

Trubion Trubion was a publicly held biopharmaceutical company that was focused on creating a pipeline of protein-based therapeutic product candidates to treat autoimmune and inflammatory diseases and cancer. Trubion was acquired by Emergent BioSolutions ...

and are now being developed by

Emergent BioSolutions Emergent BioSolutions Inc. is an American multinational specialty biopharmaceutical company headquartered in Gaithersburg, Maryland. It develops vaccines and antibody therapeutics for infectious diseases and opioid overdoses, and it provides m ...

, which acquired Trubion in 2010.

Structure

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 A single-chain variable fragment (scFv) is not actually a fragment of an antibody, but instead is a fusion protein of the variable regions of the heavy (VH) and light chains (VL) of immunoglobulins, connected with a short linker peptide of ten ...

(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 In biology, a monotypic taxon is a taxonomic group (taxon) that contains only one immediately subordinate taxon. A monotypic species is one that does not include subspecies or smaller, infraspecific taxa. In the case of genera, the term "unispec ...

, 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 B-lymphocyte antigen CD20 or CD20 is expressed on the surface of all B-cells beginning at the pro-B phase ( CD45R+, CD117+) and progressively increasing in concentration until maturity. In humans CD20 is encoded by the ''MS4A1'' gene. This gene ...

targeting SMIP under research for

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are invol ...

, and TRU-016, a CD37 targeting potential treatment for chronic lymphocytic leukemia and other B-cell cancers.TruEmergent
TRU-016 for the Treatment of B-Cell Malignancies

Production

A monoclonal antibody targeting the desired antigen can be developed the classical way, using hybridoma technology. The scFv is then constructed from the antibody's variable regions. A large number of different hinge regions and effector domains are taken from libraries of immunoglobulins, and the combined proteins are produced in genetically modified ( transfected) cells and screened for clones with useful properties like high binding specificity. The selected protein is multiplied in transfected cells suitable for medium- or large-scale production, for example

Chinese hamster ovary cell Chinese hamster ovary (CHO) cells are an epithelial cell line derived from the ovary of the Chinese hamster, often used in biological and medical research and commercially in the production of recombinant therapeutic proteins. They have found wide ...

s, and purified by

chromatography In chemical analysis, chromatography is a laboratory technique for the separation of a mixture into its components. The mixture is dissolved in a fluid solvent (gas or liquid) called the ''mobile phase'', which carries it through a system ( ...

References

{{Engineered antibodies Monoclonal antibodies