Development of a novel endometriosis treatment using a targeted viral immunotherapy
Lead supervisor: Dr Jennifer Southcombe
Co-supervisors: Professor Katy Vincent, Professor Christian Becker
Commercial partner: Accession Therapeutics
Endometriosis is a common, debilitating condition affecting >190 million women globally. Key symptoms are pain and infertility. Endometriosis is a chronic neuroinflammatory condition where lesions containing tissue resembling the uterine lining are found outside of the uterus, most commonly on the peritoneum (the pelvis lining), but also on ovaries, bladder, bowel and other more distant sites. Lesions likely develop after retrograde menstruation of endometrial epithelial cells. Despite inflammation lesions are not cleared, and current clinical management involves hormonal therapies to limit growth combined with excision/ablation of the lesions through surgery (with high risk of recurrence and surgical complications). There is no cure and novel therapies are desperately required.
Trocept, licenced by Accession Therapeutics, www.accessiontherapeutics.com, is a unique viral technology designed to deliver a broad and potent payload into cells expressing αvβ6 integrin. In preliminary collaborative work between Accession Therapeutics and Oxford University, we have discovered that αvβ6 integrin is also expressed by epithelium cells in endometriosis lesions (this is a novel finding, revealing a potential new therapeutic target for endometriosis).
This ambitious project will build high-quality capacity in an emerging priority area of precision medicine (aligned with the MRCs remit) by developing and utilising pre-clinical in vitro models to assess the therapeutic potential of Trocept for the treatment of endometriosis. The industrial partner, Accession Therapeutics, will develop Trocept vectors containing bi-specific antibodies to trigger T cell directed immunity towards endometriosis lesions. The Southcombe group in NDWRH, have established protocols for the generation of organoids from endometriosis lesion tissue. The primary objective of this project will be to investigate Trocept’s potential to infect endometriosis organoids and deliver payloads. By integrating peripheral blood immune cells to the model, as has been successfully demonstrated for multiple tumour-organoid systems, we will determine efficacy for T cell mediated killing of lesion epithelial cells. This will provide essential data for clinical translation. Milestones are i) develop Trocept vectors containing bispecific antibodies with Accession Therapeutics, ii) dose dependent delivery to endometriosis organoids/determine payload expression, iii) autologous PBMC incorporation into organoid model, iv) cytotoxicity screening of T cell directed killing of lesion epithelium.
In parallel to the laboratory project a Patient and Public Involvement (PPI) Advisory Group will be established to help inform product development. Key questions include assessment of patient acceptability of this reappropriated cancer-specific therapeutic.
This will be a new research theme for Accession Therapeutics whose main focus has been to develop onco-immune therapies. Treatment options for endometriosis are limited, and this provides an exciting opportunity to reappropriate a novel therapeutic for endometriosis. The work will be undertaken in the internationally acclaimed specialist centre for ‘Endometriosis Care and Research’ (EndoCaRe), www.wrh.ox.ac.uk/research/endometriosis-care. The team lead wide ranging projects aiming understand the mechanisms of disease, and develop diagnostics and therapeutics. Supervisors have specialist expertise required for the success of this studentship, Southcombe‘s laboratory group research immunity and cellular mechanisms of endometrial pathologies, Vincent is an honorary consultant gynaecologist and expert on gynaecological pain and Becker is a consultant gynaecologist, endometriosis specialist and co-director of EndoCaRe.
Apply using course: DPhil in Women's and Reproductive Health
