Applying fibroblasts’ newly recognized role as immune sentinels
Discoveries made by our founders and other researchers in recent years show that fibroblasts, cells long known for their structural role in both health and disease, surprisingly also have a far-reaching influence on the primary players of the immune system, including T cells, B cells, dendritic cells and macrophages.
We’re developing new treatments that modulate these fibroblast-driven immune conversations, with the goal of increasing anti-cancer immune activity in the tumor microenvironment or diminishing the overactive immune response in inflammatory diseases.
Activated fibroblasts in disease
Through single-cell sequencing and other high-resolution technologies, our founders identified previously unknown activated fibroblast populations that share features of immune cells and actively influence immune effector cells in disease. Fibroblast-immune interactions are implicated as drivers of disease in multiple solid tumors, rheumatoid arthritis, scleroderma, inflammatory bowel disease, lupus and Sjogren’s syndrome.
In tumors, activated fibroblasts contribute to an immunosuppressive environment, interfering with response to checkpoint inhibitors. Specialist fibroblast populations also drive the creation of tertiary lymphoid structures which have been associated with improved outcomes in cancer patients.
In chronic inflammatory diseases, activated fibroblasts influence immune activity both directly and indirectly, in addition to playing a key role in structural remodeling and tissue integrity. Image of an inflamed joint, courtesy of Dr Jenny Marshall and Dr Triin Major.
Advancing therapies to patients
Our approach signals a new era in immunotherapy. We’re urgently progressing a portfolio of sophisticated first-in-class antibody programs towards the clinic. We are also exploring important new targets in fibroblast-immune biology ourselves and in partnership with others.
Our activities are underpinned by highly specialist data analytics, complex tissue assays, human tissue focus and a deep understanding of antibody engineering.
Oncology: Reshaping the tumor environment
As a primary component of the stroma surrounding tumors, activated fibroblasts play a major role in shaping the environment in which cancers grow. Our goal is to reshape the tumor microenvironment, to enable the body’s immune system to better attack and destroy the tumor. Leveraging new insights into fibroblast-immune biology, our unique therapies are designed to result in improved immune cell infiltration and anti-cancer activity.
Inflammatory diseases: Promoting resolution
Activated fibroblasts can both promote and suppress immune activity in inflammatory diseases by signaling immune cells. By understanding these communications, we are developing approaches to reduce inflammation and autoimmune activity.
In 2021 Mestag entered into a target discovery collaboration with Janssen Biotech, Inc. The collaboration leverages Mestag’s specialist fibroblast sub-population biology platform and state-of-the-art data analytics to identify novel therapeutic targets. We also partner extensively with academic institutions worldwide and with leading CROs.
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