News
Micromet Presents New Anti-IL-2 Antibody with Unique Mode of Action
Potential against Inflammatory Diseases, T Cell Leukemia and Transplant Rejection
Micromet, Inc., a biopharmaceutical company focusing on the development of novel, proprietary antibody-based products for cancer, inflammatory and autoimmune diseases, is developing a monoclonal antibody inhibiting IL-2 signaling as potential novel immunosuppressant. Preclinical data on the compound, designated MT204, were now published online in the journal Molecular Immunology.
The inhibitory effect of MT204 was studied in vitro in comparison to Zenapax® (daclizumab), a marketed therapeutic antibody, which interferes with the IL-2 pathway by blocking the high-affinity CD25 subunit of the IL-2 receptor complex on T cells. Both antibodies were equally effective in inhibiting activation and proliferation of human T cells carrying the CD25 subunit. However, the data suggest that MT204 may be far superior in preventing proliferation of NKL lymphoma cells and primary natural killer (NK) cells, which do not express CD25 as part of their IL-2 receptor. Moreover, it was shown that MT204 could effectively impede IL-2 signaling events even after IL-2 was bound to its receptor on CD25-positive cells.
Based on these findings, Micromet researchers believe that MT204 may act in a dual manner: Firstly, it neutralizes IL-2 and thereby prevents binding of the cytokine to cells bearing the intermediate affinity IL-2 receptors, which lack the CD25 subunit. Secondly, MT204 binds to IL-2 already complexed with the CD25 subunit of the high affinity IL-2 receptor in a fashion that antagonizes downstream signaling and cellular responses to IL-2 by CD25-expressing cell types.
"To our knowledge, MT204 currently is the only inhibitory antibody against the IL-2 cytokine under development. We have carefully selected the antibody to interfere with the IL-2 pathway in a dual fashion," Patrick Baeuerle, CSO of Micromet, Inc. comments. "This mode of action and the choice of IL-2 as a target differentiates the compound from existing products in this space."
Micromet's most advanced product candidate is MT201 (adecatumumab), a human antibody, that has completed two Phase 2 trials in prostate cancer and in metastatic breast cancer as a single agent, respectively. MT201 is being developed in collaboration with Serono. Micromet's second product candidate in clinical trials is MT103 (MEDI-538), a BiTE® compound, currently in a Phase 1 clinical trial in non-Hodgkin's lymphoma (NHL) in Europe. Micromet's partner MedImmune has recently submitted an IND to the FDA to initiate clinical trials of MT103 in NHL in the United States.