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 |