- New preclinical data indicate IL-27 induces a gene expression signature that has been associated with resistance to chemotherapy, radiotherapy, and checkpoint inhibition -
- Findings support the ongoing clinical investigation of SRF388 in multiple tumor types -
“IL-27 is a key regulator in the immunosuppressive environment of a variety of tumors, and it can counteract T cell reinvigoration seen after PD-(L)1 pathway inhibition, thus preventing T cells from attacking the cancer cells,” said
Summary of key data:
- IL-27 induces the expression of several immunoregulatory receptors (e.g., PD-L1, TIM-3, LAG-3, and TIGIT) and reduces inflammatory cytokine production
- An IFN-stimulated gene signature is expressed in a variety of human tumors and associated with resistance to cancer therapies including chemotherapy, radiotherapy, and immune checkpoint inhibition. These IFN-stimulated genes are also upregulated by IL-27.
- IL-27 and Type 1 interferons (IFNα2, IFNβ1) counteract the immune cell reinvigoration seen after PD-(L)1 pathway blockade in human PBMCs, while IFNγ does not.
- Loss of IL-27 function, through either genetic deficiency or pharmacologic inhibition by SRF388, a first-in-class anti-IL-27 monoclonal antibody, leads to tumor growth inhibition in mouse models and early clinical data have shown monotherapy activity of SRF388 in patients with cancer (NCT04374877).
Poster presentation details:
- Title: IL-27 Inhibits Immune Cell Reinvigoration Mediated by PD-(L)1 Blockade and Induces a Type 1 Interferon Gene Expression Signature Associated with Resistance to Therapy in Cancer Patients
- Poster number: 297
- Virtual presentations:
Wednesday, September 14, 2:00 - 3:30 pm HST/ 8:00 - 9:30 pm EDTand Thursday, September 15, 8:00 - 9:30 am HST/ 2:00 - 3:30 pm EDT
- In-person session:
Thursday, September 22, 4:00 - 5:30 pm HST
The poster can also be found on Surface Oncology’s website.
SRF388 is a fully human anti-IL-27 antibody designed to inhibit the activity of this immunosuppressive cytokine.
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.
Source: Surface Oncology, Inc.