2023 Post-doctoral Fellowship Grant

Theophilos Tzaridis, Recipient

Sanford Burnham Prebys Medical Discovery Institute

Mentor: Robert Wechsler-Reya

CD155 as a Novel Regulator of Cell Growth and Immune Evasion in DIPG

Abstract:

Our study aim is to develop a novel therapeutic strategy for DIPG patients by targeting a molecule called CD155. We have discovered CD155 on the surface of both human and murine DIPG cells, and our preliminary data show that inhibiting this molecule not only enhances tumour cell killing by the immune system, but also directly inhibits growth of DIPG cells. To understand the former, we will analyse proteins secreted by those immune cells and study how they change in response to antibodies that block CD155. To understand the latter, we will study the genes that change in tumour cells after treatment with antibodies targeting CD155. That will help us understand how this two-pronged approach works and how best to use it to advance therapies for DIPG patients.

To test whether treatment with anti-CD155 antibodies is an effective therapy for DIPG, we will treat tumour-bearing mice with these antibodies and study their tumour growth and survival. Notably, it is unclear if anti-CD155 antibodies can cross the blood-brain barrier and enter the tumour. Therefore, we will compare the efficacy of administering the antibody via three different routes: 1. Systemic injection into the abdomen of the mouse, 2. Injection into the cerebrospinal fluid and 3. Injection into the tumour itself. These studies will not only increase our understanding of DIPG biology but will also pave the way for improved immunotherapies for patients with this devastating disease.