Small modular immunopharmaceutical

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Small modular immunopharmaceuticals, or SMIPs for short, are artificial

antibodies (immunoglobulins), and like them have a binding site for antigens that could be used for monoclonal antibody therapy. SMIPs have similar biological half-life and, being smaller than antibodies, are reasoned to have better tissue penetration properties. They were invented by Trubion and are now being developed by Emergent BioSolutions, which acquired Trubion in 2010.[1]

Structure

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.[2]

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,[3] and TRU-016, a CD37 targeting potential treatment for chronic lymphocytic leukemia and other B-cell cancers.[4][5]

Production

A monoclonal antibody targeting the desired antigen can be developed the classical way, using

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 cells, and purified by chromatography.[2]

References

  1. ^ TruEmergent: SMIP Therapeutics Archived 2011-08-22 at the Wayback Machine
  2. ^
    PMID 17440052
    .
  3. PMID 20140823
    .
  4. PMID 19943209
    .
  5. ^ TruEmergent: TRU-016 for the Treatment of B-Cell Malignancies Archived 2011-08-22 at the Wayback Machine
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