– Study reveals the structural basis of receptor activation and signaling by IL-27 cytokine –
– Study elucidates how SRF388 binds to IL-27 to prevent interaction with the IL-27 receptor, inhibiting the cytokine’s signaling activity –
– Findings support the ongoing clinical investigation of SRF388 –
FLANDERS, Belgium and CAMBRIDGE, Mass., Oct. 19, 2022 (GLOBE NEWSWIRE) -- VIB, Flanders’ leading life sciences institute, and Surface Oncology (Nasdaq: SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, today announced jointly the publication of a study entitled, “Structural basis of activation and antagonism of receptor signaling mediated by interleukin-27: Cell Reports,” in Cell Reports, a leading scientific journal. The study was a collaborative research effort between the Unit for Structural Biology at the VIB-University of Ghent Center for Inflammation Research and Surface Oncology.
“In this study, we have shown how the IL-27 heterodimer is formed, and how the cytokine uniquely docks with its receptor to form the IL-27 signaling complex, providing new insights into IL-27 cytokine biology,” said Savvas Savvides, Professor and Group Leader at Ghent University and the VIB Center for Inflammation Research. “The elucidation of the structure of IL-27 and its complex with its signaling receptor provides invaluable data to support the ongoing mechanistic interrogation, engineering, and therapeutic targeting of IL-27.”
“SRF388 is a fully human anti-IL-27 antibody designed to inhibit the activity of this immunosuppressive cytokine, and this study provides important structural evidence that the antibody directly competes with the IL-27 receptor to prevent downstream signaling of the cytokine,” said Vito Palombella, Chief Scientific Officer at Surface Oncology. “IL-27 has been implicated as an immunosuppressive cytokine in several tumor microenvironments and understanding the mechanistic basis of SRF388’s inhibitory activity will help inform its ongoing clinical development.”
Summary of key data:
- IL-27 is comprised of p28 and EB13 subunits which are uniquely organized into a heterodimeric assembly distinct from other members of the IL-12 family of cytokines.
- The elucidated crystal structure of IL-27 and its receptor reveals the presence of at least 4 different sites that are important for the assembly of the signaling complex and which potentially can be used as targeting sites to disrupt IL-27’s structure and subsequently its immunosuppressive function.
- Analyses reveal that SRF388 and the IL-27 receptor contend for the same binding epitope on IL-27, with SRF388 competitively inhibiting IL-27 receptor activity, providing structural evidence for SRF388’s potent antagonistic properties.
Details on the study by Katarzyna Składanowska, Yehudi Bloch et al. can be found in the October 18 issue of Cell Reports [VOLUME 41, ISSUE 3, 111490, https://www.cell.com/cell-reports/fulltext/S2211-1247(22)01340-7. Additional authors include Daniel Aldridge and Christopher Hunter, Ph.D., chair of the Department of Pathobiology at the University of Pennsylvania School of Veterinary Medicine and a member of the Surface Oncology Scientific Advisory Board.
SRF388 is a fully human anti-IL-27 antibody designed to inhibit the activity of this immunosuppressive cytokine. Surface Oncology has identified particular tumor types, including liver, kidney and lung cancer, where IL-27 appears to play an important role in the immunosuppressive tumor microenvironment and may contribute to resistance to treatment with checkpoint inhibitors. SRF388 targets the rate-limiting p28 subunit of IL-27, and preclinical studies have shown that treatment with SRF388 blocks the immunosuppressive biologic effects of IL-27, resulting in immune cell activation in combination with other cancer therapies including anti-PD-1 therapy, as well as potent anti-tumor effects as a monotherapy. Furthermore, Surface Oncology has identified a potential biomarker associated with IL-27 that may be useful in helping to identify patients most likely to respond to SRF388. In November 2020, Surface announced that SRF388 was granted Orphan Drug designation and Fast Track designation for the treatment of refractory hepatocellular carcinoma from the FDA.
VIB’s core mission is to generate disruptive insights in the molecular underpinning of life and to translate these actively into impactful innovations for patients and society. VIB is an independent research institute where some 1,800 top scientists from Belgium and abroad conduct pioneering basic research. As such, they are pushing the boundaries of what we know about molecular mechanisms and how they rule living organisms such as human beings, animals, plants, and microorganisms. Based on a close partnership with five Flemish universities – Ghent University, KU Leuven, University of Antwerp, Vrije Universiteit Brussel, and Hasselt University – and supported by a solid funding program, VIB unites the expertise of all its collaborators and research groups in a single institute. VIB’s technology transfer activities translate research results into concrete benefits for society such as new diagnostics and therapies and agricultural innovations. These applications are often developed by young start-ups from VIB or through collaborations with other companies. This also leads to additional employment and bridges the gap between scientific research and entrepreneurship. VIB also engages actively in the public debate on biotechnology by developing and disseminating a wide range of science-based information. More info can be found on www.vib.be.
About Surface Oncology
Surface Oncology is an immuno-oncology company developing next-generation antibody therapies focused on the tumor microenvironment. Its pipeline includes two wholly-owned clinical-stage programs targeting CD39 (SRF617) and IL-27 (SRF388), as well as a preclinical program focused on selectively depleting regulatory T cells in the tumor microenvironment via targeting CCR8 (SRF114). In addition, Surface has two partnerships with major pharmaceutical companies: a collaboration with Novartis targeting CD73 (NZV930; Phase 1) and a collaboration with GlaxoSmithKline targeting PVRIG (GSK4381562, formerly SRF813; Phase 1). Surface’s novel, investigational, cancer immunotherapies are designed to achieve a clinically meaningful and sustained anti-tumor response and may be used alone or in combination with other therapies. For more information, please visit www.surfaceoncology.com.
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Source: Surface Oncology, Inc.