On November 7, 2022 Surface Oncology (Nasdaq: SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, reported the presentation of two posters at the 2022 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in Boston (Press release, Surface Oncology, NOV 7, 2022, View Source [SID1234623278]). The posters feature new non-clinical data for both SRF388 and for SRF114 and will be presented on Friday, November 11, 2022.
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"We are very pleased to share intriguing new non-clinical data that suggest there is immune-suppressive cross-talk between IL-27 and PD-L1 expression within the tumor microenvironment," said Vito Palombella, PhD, Chief Scientific Officer, Surface Oncology. "Immunohistochemical analysis of IL-27, the IL-27 receptor, and PD-L1 shows co-localization across several cancer types, and in vitro studies have shown that IL-27 can directly upregulate PD-L1 expression on both immune and tumor cells. These data support our ongoing clinical studies evaluating SRF388, our first-in-class, fully human anti-IL-27 antibody, in combination with pembrolizumab."
Dr. Palombella added, "We also are pleased to share new SRF114 data which demonstrate the antibody’s ability to selectively deplete tumor Treg cells. We believe the selective depletion of intratumoral Treg cells provides a mechanism to inhibit tumor growth independent of checkpoint inhibition, as we have shown in our preclinical models. We look forward to investigating the safety and efficacy of SRF114 in a Phase 1 clinical trial."
SITC Poster Presentations:
Title: IL-27 expressed in the tumor microenvironment is correlated with PD-L1 levels and can induce PD-L1 expression on immune and tumor cells
Poster/Abstract: 1082
Session Type/Title: Immune-stimulants and immune-modulators
Session Date and Time: Friday, November 11 from 9 a.m.– 8:30 p.m.
Summary of key data:
Primary tumor samples from several cancers including lung, liver, renal, gastric, and head and neck, have IL-27+ tumor associated macrophages (TAMs).
IL-27-expressing TAMs are localized within the vicinity of PD-L1+ tumor cells in lung and liver cancers, with the highest IL-27+ density being associated with the highest PD-L1 expression.
IL-27 can regulate PD-L1 expression in immune cells and tumor cell lines.
Title: SRF114, an afucosylated anti-CCR8 antibody, depletes intratumoral Treg cells and reduces tumor growth
Abstract/Poster: 1388
Session Type/Title: Novel Single-Agent Immunotherapies
Session Date and Time: Friday, November 11 from 9 a.m.– 8:30 p.m.
Summary of key data:
CCR8 expression is highest on intratumoral regulatory T (Treg) cells compared to peripheral Tregs and other immune cells.
SRF114 treatment results in dose-dependent activation of immune cells, including natural killer (NK) cells and monocytes.
In dissociated tumor cultures, SRF114 selectively depletes Treg cells and has limited impact on effector T cells; in a mouse model, SRF114 treatment significantly reduces tumor growth and depletes intratumoral Treg cells, with minimal impact on peripheral Tregs.
The posters will be available on Surface Oncology’s website on November 10, 2022.
About SRF388
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 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.
About SRF114
SRF114 is a fully human, afucosylated anti-CCR8 antibody designed to preferentially deplete CCR8+ Treg cells within the tumor microenvironment. In pre-clinical studies, Surface Oncology has shown that SRF114 induces antibody-dependent cellular cytotoxicity (ADCC) and/or antibody-dependent cellular phagocytosis (ADCP) pathways to deplete intratumoral Treg cells. In addition, SRF114 reduced tumor growth in murine models. These findings support the advancement of SRF114 as a therapeutic candidate that holds the potential to drive anti-tumor immunity in patients.