Modeling follicular lymphoma in chicken embryos to personalize therapeutic decision – FLINOVO

Follicular lymphoma (FL) is the most frequent indolent lymphoma. Even if the overall survival is prolonged for the majority of the patients, a fraction of them does not respond well to first line treatment and has a poor prognosis. However, current prognostic tools are not robust enough to identify prospectively these patients. Moreover, many targeted therapies are being developed in lymphomas, but most of them are active in only a fraction of the patients, and we are still not able to predict which treatment will be optimal for a given patient.
Here we propose to establish a model patient derived tumour xenograft (PDX) in chicken embryos for FL. Our preliminary results obtained with three FL samples from three different patients show that all patients tumours engraft. The detailed analysis of the engrafted tumours displays an expansion of the malignant cells, and a conservation of the clonal architecture. Interestingly, the in ovo PDX model allows the testing of chemosensitivity in a few days, as already demonstrated with various cancer types and multiple drugs.
Thanks to this model, we will address different challenges which are unmet medical need to improve the care of patients with follicular lymphoma:
- identification of the patients who respond poorly to immunochemotherapy. We will analyse the response to rituximab-chemotherapy in 30 PDX from 15 patients with poor clinical response to treatment and 15 patients with very good response to treatment. By comparing the tumour response in ovo with clinical outcome, we will evaluate the predictive potential of the model.
- identification of the patients who might respond to a targeted therapy, by testing the effects of a panel of targeted therapies relevant in lymphoma on the 30 PDX and looking for heterogeneity of response in the cohort. This model could be very interesting for future clinical trials, by enabling the prospective identification of patients with the highest probability to respond.
- identification of the tumour cells responsible for the late relapses of the disease by performing iterative transplantation experiments and integrative single cell analysis. We will also address the role of the tumour microenvironment by analysing the impact of the depletion of different cell types on tumour engraftment and growth.

This project is headed by an academic researcher involved in the French clinical group for clinical trials in lymphomas (LYSA), and belonging to the Carnot Institute Calym which is devoted to the promotion of translational research in lymphoma. The industrial partner is the inventor of the in ovo model. We expect important scientific advances with this project (first model of primary human follicular lymphoma). We can also underline its strong potential of valorisation, particularly for the screening of patients for clinical trials.