Friday, December 11, 2015

CGEN-15001 at the ACR 2015 Meeting in San Francisco

There has been one publication on CGEN-15001 at the ACR 2015 Annual Meeting in San Francisco. “CGEN-15001 is an Fc fusion protein composed of the extracellular domain of a novel B7-like protein.” The B7 proteins are found on activated APCs (antigen presenting cells). Interestingly B7 may act coinhibitory and costimulatory. CGEN-15001 has already appeared with mouse model studies at the ACR meetings in 2012 and 2014; please look under references. CGEN-15001 haa shown efficacy in these mouse models of rheumatoid arthritis and psoriasis.

Iris Hecht and colleagues presented: “CGEN-15001, a Novel B7-like Protein, Controls Inflammation in a Translational Rheumatoid Arthritis (RA) Assay and Induces Treg Driven Long-Term Remission in an Autoimmune Disease Model”. In “Background” we read: “The therapeutic potential of CGEN-15001 for RA was studied in co-cultures of cytokine activated T cells (TcK) and macrophages (Mϕ) from RA patients and healthy donors. Such co-cultures mimic the interaction of cells in RA synovium that lead to aberrant cytokine production and provide a translational tool to evaluate potential therapies.” Methods: “CD4+ T cells and monocytes were isolated from healthy donors or RA patients’ blood and cultured for 6 days with TNFα, IL-6 and IL-15 to induce TcK or with M-CSF to induce Mϕ differentiation, respectively. Autologous TcK and Mϕ were co-cultured in the presence of CGEN-15001 or controls for 24hrs. Cytokines were evaluated by luminex. […]” Results: “In synovial-like Mϕ: TcK co-cultures, CGEN-15001 abrogated secretion of pro-inflammatory cytokines including TNFα, IL-17, IFNγ, GM-CSF, RANTES and MIP-1α. Similarly, inhibition in TNFα secretion was observed in co-cultures from RA patients’ cells. […]” I’ve omitted the parts on an experimental autoimmune encephalomyelitis. Conclusion: “The anti-inflammatory activity of CGEN-15001 in a translational assay mimicking RA synovium supports its therapeutic potential in RA. The long remission maintained by active Tregs in the EAE model supports a novel mechanism of re-establishing tolerance to autoantigens. Therefore, these results support the therapeutic potential of CGEN-15001 to reduce inflammation and maintain long-term remission in autoimmune diseases and RA in particular.”

These results are complicated, but as activated t-cells and macrophages play a crucial role in synovial inflammation, CGEN-15001 is a promising drug candidate for rheumatoid arthritis but also other autoimmune diseases. I hope that Compugen will start phase 1 studies soon.

Iris Hecht, Kay McNamee, Ilan Vaknin, Anat Oren, Joseph R. Podojil, Galit Rotman, Eyal Neria, Stephen D. Miller and Richard O. Williams: CGEN-15001, a Novel Negative Costimulatory Fusion Protein Is Effective in the Collagen-Induced Arthritis Mouse Model of Rheumatoid Arthritis. 2012 ACR/ARHP Annual Meeting:
Iris Hecht, Kay McNamee, Aviad Keren, Joseph R. Podojil, Ilan Vaknin, Anat Oren, Galit Rotman, Eyal Neria, Stephen D. Miller, Amos Gilhar and Richard O. Williams: CGEN-15001, a Novel Immunomodulatory Fusion Protein of the B7 Family Induces Immune Tolerance and Shows Efficacy in Mouse Models of Rheumatoid Arthritis and Psoriasis. 2014 ACR/ARHP Annual Meeting:
Hecht I, Gilmour A, Tange C, McIntyre D, Podojil JR, McNamee K, Rotman G, Neria E, Kurowska-Stolarska M, Williams RO, Miller SD, McInnes IB. CGEN-15001, a Novel B7-like Protein, Controls Inflammation in a Translational Rheumatoid Arthritis (RA) Assay and Induces Treg Driven Long-Term Remission in an Autoimmune Disease Model [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). Accessed December 11, 2015.


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