Small modular immunopharmaceutical

Small modular immunopharmaceuticals (also known as “small modular immunopharmaceuticals”), or SMIPs for short , are artificial proteins derived from antibodies . They have a modular structure and, like antibodies, consist of an antigen- recognizing protein domain , a flexible joint domain (hinge domain) and an effector domain. Compared to antibodies, they have a significantly lower molecular weight and thus improved biopharmaceutical properties. Because of their ability to recognize certain protein structures and then to trigger specific reactions in the organism, small modular immunopharmaceuticals have been and are currently being tested in clinical studies as potential novel drugs, among other things for the treatment of chronic inflammatory diseases and cancer . Small modular immunopharmaceuticals were largely developed by the biotechnology company Trubion , which was acquired by Emergent BioSolutions in 2010 .

structure

Small modular immunopharmaceuticals have a modular structure and consist of three domains. Depending on the modules used, Small modular immunopharmaceuticals can have different structural properties. ScFv antibodies are used as antigen-recognizing domains . These are significantly smaller than the antigen-recognizing variable domains of conventional antibodies. The C _H 2 and C _H 3 domains of immunoglobulin G ₁ (IgG ₁ ) , for example, are suitable as effector domains . The antigen recognition and effector domains are linked to one another in a single protein strand via a hanging domain, which can also be borrowed from an immunoglobulin . Small modular immunopharmaceuticals built in this way, including the TRU-015 and TRU-016 currently in clinical trials, are produced by the cell lines used for production as dimers with an antibody-like structure. These dimeric small modular immunopharmaceuticals have a simpler structure than the conventional IgG-type antibodies, which consist of four protein strands, and their molecular mass is about 30% lower.

Manufacturing

Small modular immunopharmaceuticals are developed according to their modular structure. The antigen-recognizing component can be borrowed from a monoclonal antibody specific for the target structure and transferred into an scFv antibody. The remaining components come from a library consisting of various hinge and effector domains. The fragments are combined with the help of molecular biological methods. The optimal combination of antigen binding, hinge and effector domains can be determined with the help of suitable screening methods.

Web links

truemergent.com: Small Modular ImmunoPharmaceutical (SMIP ™) drug assembly technology ( Memento of November 8, 2011 in the Internet Archive ) (manufacturer information about the SMIP technology)

Individual evidence

↑ ^a ^b Rubbert-Roth A: TRU-015, a fusion protein derived from an anti-CD20 antibody, for the treatment of rheumatoid arthritis . In: Curr. Opin. Mol. Ther. . 12, No. 1, February 2010, pp. 115-23. PMID 20140823 .
↑ ^a ^b Robak T, Robak P, Smolewski P: TRU-016, a humanized anti-CD37 IgG fusion protein for the potential treatment of B-cell malignancies . In: Curr Opin Investig Drugs . 10, No. 12, December 2009, pp. 1383-90. PMID 19943209 .

[Rubbert-Roth_A_(2010)-1] Rubbert-Roth A: TRU-015, a fusion protein derived from an anti-CD20 antibody, for the treatment of rheumatoid arthritis . In: Curr. Opin. Mol. Ther. . 12, No. 1, February 2010, pp. 115-23. PMID 20140823 .

[Robak_T_et_al._(2009)-2] Robak T, Robak P, Smolewski P: TRU-016, a humanized anti-CD37 IgG fusion protein for the potential treatment of B-cell malignancies . In: Curr Opin Investig Drugs . 10, No. 12, December 2009, pp. 1383-90. PMID 19943209 .