Novel Transcription Factor - FOXP1 and Uses Thereof - Isis Project No 0634 and 1368
Research at the University of Oxford has resulted in the identification of a novel transcription factor, FOXP1. Unlike other subgroups of this family, the FOXP genes contain both the forkhead/winged helix DNA binding domain together with a Cys2-His2 zinc finger. The FOXP1 protein may function as a co-regulator of nuclear receptors, and in particular the oestrogen receptor. The gene encoding FOXP1 has been sequenced, and a monoclonal antibody raised against the protein.
Applications
Potential applications of this technology include early diagnosis and use as a prognostic indicator of lymphomas, leukaemias and carcinomas. Therapeutic applications may be developed through modulating the humoral or cellular functions of the immune system and development of treatments which either modulate or normalise the levels of FOXP1 expression in cancers and autoimmune diseases (including rheumatoid arthritis and multiple sclerosis). Preliminary studies suggest that FOXP1 expression may be associated with poor response to therapy in lymphoma and breast cancer patients making this molecule a potential drug target in these cancers.
Background
Transcription factors have essential roles in regulating gene expression. The forkhead/winged helix (FOX) family of transcription factors play important roles in normal development, including regulating cellular proliferation, differentiation, signal transduction, mitotic program, longevity and cellular transformation. In addition to their normal roles, members of this family also play a part in mammalian oncogenesis.
The Oxford Invention
Tissue localisation studies of FOXP1 have been performed using an antibody raised against this novel protein. FOXP1 is expressed in most normal healthy tissues. When studied in cancerous tissues, however, abnormal levels of nuclear protein expression were identified in a wide range of both solid tumours and haematological malignancies. In addition, changes in FOXP1 expression have been shown to occur early during malignant progression, often before histological changes. Increased expression of FOXP1 mRNA has also been found in the peripheral blood fractions of patients suffering from idiopathic thrombocytopenia purpura and multiple sclerosis.
Commercialisation Opportunity
These technologies will be of interest to companies developing diagnostic and prognostic tests for developmental defects, cancer and autoimmune diseases, and to companies developing therapeutic agents for the treatment of such conditions. These exciting new discoveries are the subject of 2 patent applications (WO 01/40303 A1, and another recent GB priority filing), and some of the data has been published (Cancer Research 61, 8820-8829, 2001). Isis Innovation is actively seeking partners to commercialise this technology.
Keywords
FOXP1, transcription factor, cancer, autoimmune disease, rheumatoid arthritis, prognosis, therapy