Simon Brunel, Ph.D.

What if we had one therapy that could cure all autoimmune diseases?

FUNDED BY: The generosity of The Rosemary Kraemer Raitt Foundation Trust, John and Cim Kraemer and 2020 Various Donors.

What was the goal of your SPARK project?

The overall aim of this project is to validate a new cell therapy protocol in mice to induce immune tolerance to a given antigen using the thymus as a target. This tolerance could be used to counteract the immune response that occurs in some gene therapy protocols or to reinitiate thymic tolerance to self-antigens. Given the well-established role of the chemokine receptor CCR9 in directing migration of peripheral dendritic cells (DCs) to the thymus and their role in tolerance induction, we hypothesized that the expression of an antigen conveyed in the thymus by genetically-modified DCs will impact T cell selection in the thymus, hence the immune response to this antigen in the periphery.

Did you face any challenges?

The global world shortage of goods did not spare science reagents and supplies. Delivery delays impacted the schedule of my experiments. Using a mouse model for my experiments required a lot of ethical writing and protocol approval that also significantly impacted my timeline and scheduled experiment. Due to these delays, I was granted a six month extension on my project and look forward to providing a final update this fall.

SPARK project update:

Preliminary results indicate the working hypothesis might prove correct. As of today, we have obtained the functional proof in vitro that CCR9 expression on genetically-modified BMDC (bone marrow dendritic cells derived) improves their migration in response to the CCL25 ligand. With that knowledge, we undertook in vivo experiments with modified DCs injected into congenic mice. We observed a higher thymus to spleen ratio in terms of frequency of BMDC cells of donor origin if those were modified by a CCR9-expressing vector, suggesting that modified DCs preferentially migrated to the thymus compared to unmodified DCs. Although the numbers of detected cells are still low, we think that the protocol can be improved. Notably, we began our investigation using the luciferase reporter gene to monitor cell migration in vivo in live animals. The therapeutic phase of this project has been challenging, but encouraging results should be available soon and I look forward to providing a final update this fall.

What’s next for this project?

More experiments on preclinical models are currently running. We are expecting very encouraging results soon, and we believe they will extend the diversity of preclinical models. Those results combined will hopefully lead to a breakthrough publication that will attract more grant funding. In the long term, I’m hoping biotech companies will be interested in developing this methodology of immune system editing.

What’s next for Simon?

I am now starting my fourth year as postdoc at LJI. This is usually the year that entails publication and finalizing projects. In order to carry my SPARK project as far forward as possible, I’m currently building skills that will be required to lead this project at a company or startup.