How it works
- TNFRSF25 is highly and constitutively expressed on resting FoxP3+ T regulatory (Treg) cells.
- TNFRSF25 recognizes the cytokine TNF-like ligand 1A (TL1A) secreted by several cell types including dendritic cells, monocytes, macrophages, and plasma cells.
- In the absence of a danger or activating signal, co-stimulation of TNFRSF25 results in the selective expansion of immunosuppressive FoxP3+ CD4+ Treg cells that can reduce inflammation.
- Conversely, co-stimulation of TNFRSF25 in the presence of a danger or activating signal (arising from infection or cancer) promotes the expansion of inflammatory effector T cells that play a critical role in mediating anti-tumor and anti-pathogen responses.
TNFRSF25 by the numbers
Advantages of Targeting TNFRSF25
- TNFRSF25-mediated expansion of Treg cells in the absence of a danger signal is accompanied by increased expression of immunosuppressive markers and activity.
- TNFRSF25 agonists have shown benefit in several preclinical models including rheumatoid arthritis1, diabetic retinopathy2, allergic lung inflammation3, inflammatory bowel disease4, infectious disease5, and hematopoietic stem cell transplant6-7.
- Preclinical studies demonstrate a low toxicity profile associated with TNFRSF25 targeting.
- Single agent with unique context dependent capability to enhance or suppress inflammatory immune responses.
TNFRSF25-Targeting Development Programs
- Oncology: PTX-35 is a humanized monoclonal antibody agonist of TNFRSF25 currently being evaluated in a Phase I clinical trial as an immunotherapy for the treatment of solid tumors.
- Inflammation: Preclinical studies investigating the potential of PTX-35 for restoring or protecting the immunological balance in multiple inflammatory disorders are underway.