This project, entitled "Targeting the TSP-1/CD47 axis to restore anti-tumor immunity in the treatment of ovarian carcinoma" and led by Prof. Stéphane Dedieu, is based on an academic-private partnership involving our research unit, the Institut Gustave Roussy (INSERM U981, Dr. Alexandra Leary) and the biotechnology company Apmonia Therapeutics (Dr. Albin Jeanne).
Due to the non-specific nature of symptoms and its late diagnosis, ovarian cancer remains of poor prognosis and its incidence continues to progress. Current therapeutic options leave room for recurrence in 80% of cases and there remains a real and urgent need to identify new therapeutic targets, particularly in immuno-oncology, and to propose innovative combinatorial therapies. Among the potential targets, thrombospondin-1 (TSP-1) is a protein overexpressed in ovarian tumors, whose interaction with the CD47 receptor has recently been reported to inhibit adaptive immunity.
We have designed the first selective antagonist of the TSP-1/CD47 interaction (TAX2 peptide, patented and licensed), which has been shown to be anti-tumor in various mouse models. In particular, our data show that TAX2 induces a significant T cell-dependent anti-tumor immune response and synergizes with immune checkpoint inhibitors.
The objective of the project is to provide proof of concept of the efficacy of the TAX2 drug candidate as an immunomodulator in ovarian cancer in orthotopic syngeneic and humanized mouse models receiving patient-derived transplants. The relevance of this targeting will be validated using annotated clinical samples from large cohorts, while identifying predictive biomarkers of treatment response. The formulation of the TAX2 drug candidate will be optimized and we will provide a documented rationale for the implementation of optimized combinatorial strategies based on the therapeutic index. Finally, we will develop a rapid assay for the detection of circulating TSP-1 levels as a valuable tool for segmentation of patients likely to respond favorably to the TAX2 approach.