Mechanism of action

Knowing how your therapy acts on physiological or pathological processes allows for specific monitoring of treatment in patients. Moreover, it enables you to optimize administration of the therapy to achieve maximum efficacy. Understanding the mechanism of action may also improve patient stratification, to predict who may benefit most of the treatment.

In addition, understanding a mechanism of action precisely may also yield new indications for which the therapy may be beneficial.

What can Sanquin do for you?

Considering the extensive knowledge and expertise of Sanquin, we are your ideal partner to elucidate the mechanism(s) of action of your therapy. When you have a general idea of the working mechanism of your drug, but specific questions remain, we offer single assays to unravel aspects of the working mechanism. Alternatively, we can develop an extensive co-development trajectory, to examine the mode of action of your drug or treatment in more detail. All assays can be adapted to your specific research question and needs.

The research department of Sanquin has a profound interest in the mechanism of action of various plasma products and other immunomodulatory therapeutics. Examples of ongoing research topics include structure and function of antibodies (intravenous immunoglobulin (IVIG), glycosylation of antibodies, antibody multimer structures, IgG4, complement activation, etc.), immunogenicity of therapeutic proteins and auto-antigens (eg monoclonal antibodies, FVIII, ADAMTS13, etc.) and many more. To find out more about the research that is performed at Sanquin visit our research pages.

 

Examples

Differences in working mechanism between MPA and MTX

Mycophenolic acid (MPA) and methotrexate (MTX) are immunosuppressive drugs used for the treatment of various immunological disorders. Production of T cell cytokines in whole blood cultures, as well as in PBMC cultures, is inhibited by a low concentration of both drugs.

We elucidated that the mechanism by which inhibition is achieved, differs for the drugs. Inhibition of T cell cytokine production by MPA was more profound and started earlier compared to the inhibition by MTX. MTX induced apoptosis in T cells that became activated, whereas MPA prevented activation of T cells by arresting the cell cycle in the G0/G1 phase. The observation that MTX cannot prevent T cell activation but induces apoptosis in activated T cells, and that MPA reversibly prevents activation of T cells, could explain the immunosuppressive effects of both these drugs.

Cytokine production by monocytes was only slightly decreased by the drugs. These results indicate that T cells are the main target cells of the immunosuppressive drugs MPA and MTX. 

Also find out what our preclinical immune services can do for you.

 

References

Mycophenolic acid and methotrexate inhibit lymphocyte cytokine production via different mechanisms.
de Lathouder S, Gerards AH, de Groot ER, Valkhof M, Aarden LA. Eur Cytokine Netw. 2002 Jul-Sep;13(3):317-23 

Inhibition of cytokine production by methotrexate. Studies in healthy volunteers and patients with rheumatoid arthritis.
Gerards AH, de Lathouder S, de Groot ER, Dijkmans BA, Aarden LA. Rheumatology 2003 Oct;42(10):1189-96.