Effect of Immunosuppressants and Immune Stimulants: MIMIC® System Reproduces In Vivo Results

We conducted a study with a collaborator to assess a number of well characterized immune agents in the MIMIC® System. These included adjuvants CpG (TLR9 agonist) and Imiquimod (TLR 7/8 agonist); immunosuppressive agents cyclosporine A (IL2 inhibitor) and methotrexate (folate inhibitor); monoclonal antibodies OKT3 (T cell suppression), anti-CD154 (inhibitor of T/B cell interactions), and anti-TNFα (blocks TNFα); and the immunomodulatory fusion protein CTLA4Ig (inhibitor of co-stimulation via suppression of T cell activation). As shown in the table below, characterization of the effects of each of these agents in the MIMIC® System resulted in a profile of response in vitro in good accord with known in vivo biological activities of the various test materials.

Agent In Vivo Activity MIMIC® Activity
CpG Adjuvant Immunopotentiation
Imiquimod Adjuvant Immunopotentiation
Cyclosporine A Immunosupressant Immunosuppression
Methotrexate Immunosupressant Immunosuppression
OKT3 Initially activate T cells (cytokine release), then immunosuppressive activity targeting CD3 of T cells Th1 potentiator, Th2 antagonist, T cell proliferation
Anti-CD154 Suppresses T/B cell interaction Modest B cell immunosuppressant
CTLA4Ig Inhibits T cell activation (costimulation) T cell suppression
Anti-TNFα Blocks inflammatory activity of TNFα Modest immunosuppressant, suppresses TNFα production