We invite Kevin Boyé to give a seminar open to the scientific community.

Dr. Kevin Boyé
CRCN INSERM Paris Cardiovascular Research Center – 56 Rue Leblanc, 75015 Paris
Co-founder of D2B3 – 101 College Street, 06511 New Haven, CT, USA

“Unlocking the Blood–Brain Barrier during Glioblastoma progression”

📆 Tuesday, January 27, 2 p.m.
🚩 BBS Conference Room, 2 rue Dr Hoffmann Martinot, Carreire site, University of Bordeaux

Abstract

Blood vessels in the brain form 600 kilometers of specialized blood-brain barrier (BBB) that protect the brain from toxins and pathogens, thereby ensuring homeostasis and proper neurological function. However, BBB impermeability also severely limits brain drug delivery during many neurological disorders.

Glioblastoma (GBM) is the most aggressive primary brain tumor with a median survival of 12–15 months. Although BBB integrity is partially disrupted within the tumor core, the highly invasive nature of GBM cells into the BBB-competent brain parenchyma strongly limits the delivery and efficacy of therapeutic molecules, leading to inevitable recurrence after surgical resection. Hence, developing tailored therapeutic strategies that can transiently and safely modulate BBB permeability without compromising its protective function remains a major unmet clinical need.

We recently identified the endothelial receptor Unc5B and its ligand Netrin-1 as central regulators of BBB integrity. Single-cell RNA sequencing revealed that this pathway controls a core BBB gene expression program of over 100 genes involved in tight junction organization, nutrient and ion transport, and efflux pump function. To harness this mechanism therapeutically, we developed, optimized, and patented a fully human monoclonal antibody (Anti-Unc5B) that specifically blocks Netrin-1 binding to Unc5B.

Following intravenous injection, Anti-Unc5B induces a brain-wide and brain-specific, opening of the BBB for up to six hours, prior to barrier resealing. This transient permeability window is size-selective, cumulative and safe. Using this BBB-permeabilizing strategy, we could enhance the delivery and efficacy of a wide variety of therapeutic molecules including chemotherapies, tyrosine kinase inhibitors and nanobodies during GBM progression, resulting in increased tumor cell apoptosis, reduced tumor growth and improved survival.

Biosketch

I completed my PhD in the laboratory of Pr. Andreas Bikfalvi under the supervision of Dr. Clotilde Billottet (INSERM U1029, France), where I identified the chemokine receptor CXCR3-A and its ligand CXCL4L1 as a novel signaling pathway essential for brain tumor progression (Boyé K. et al., Nature Communications 2017; Boyé K. et al., Scientific Reports 2017; Quemener C et al. Cancer Research 2016). However, like most therapeutic molecules developed for neurological diseases, intravenously injected CXCR3-A inhibitors were unlikely to efficiently cross the blood–brain barrier (BBB).

To overcome this limitation, I joined the laboratory of Pr. Anne Eichmann at Yale University (New Haven, USA) as a postdoctoral fellow (2017-2022), where I investigated mechanisms regulating vascular barrier integrity (Genet G., Boyé K. et al. Nature Communication 2019; Zhang F. et al. Science 2018), with a particular focus on the BBB (Boyé K. et al., Nature Communications 2022). I identified the endothelial Unc5B receptor and its ligand Netrin-1 as a key signaling pathway required to maintain BBB integrity. I subsequently developed a human monoclonal antibody that block Netrin-1 binding to Unc5B, enabling a reversible and controlled BBB opening leading to brain delivery of bioactive molecules (Two Patents in 2023).

Since 2023, I am a Group Leader (CRCN) at the Paris Cardiovascular Research Center (INSERM U970). My group is currently funded by an FRM “Amorçage jeunes équipes” (2023-2026), an ANR PRC (Coordinator; 2026 – 2028) and an INCa PLBIO (Coordinator; 2026 – 2028). My research program focuses on:

1. Optimizing brain drug delivery beyond the BBB during brain tumor progression.
2. Enhancing BBB integrity in diseases with BBB dysfunction.

We recently reported a BBB gene-expression program zonated along the arteriovenous axis that can be tuned to increased brain drug delivery (Furtado et al., PNAS 2024).

In 2024 I co-founded D2B3 (https://d2b3.bio), a start-up company spun out of Yale University, aiming to improve brain drug delivery in patients using our patented BBB-permeabilization technology.