Georganaki, M. | bioRxiv Science

bioRxiv2021

Agonistic CD40 antibody therapy induces tertiary lymphoid structures but impairs the response to immune checkpoint blockade in glioma

Gliomas are brain tumors characterized by immunosuppression. Immunostimulatory agonistic CD40 antibodies (CD40) are in clinical development for solid tumors but are yet to be evaluated for glioma. Here, systemic delivery of CD40 led to cytotoxic T cell dysfunction and impaired the response to immune checkpoint inhibitors in preclinical glioma models. This was associated with an accumulation of suppressive CD11b+ B cells. However, CD40 also induced tertiary lymphoid structures (TLS). In human glioma, TLS correlated with increased T cell infiltration indicating enhanced immune responses. Our work unveils the pleiotropic effects of CD40 therapy in glioma, which is of high clinical relevance.

cancer biology↗

bioRxiv2020

A Machine Learning approach for assessing drug development risk

Characterizing drug development risk - the probability that a drug will eventually receive regulatory approval - has been notoriously hard given the complexities of drug biology and clinical trials. This often leads to an inefficient allocation of resources, and an overall reduction in R&D productivity. We propose a Machine Learning (ML) approach that provides a more accurate and unbiased estimate of drug development risk than traditional models.

bioinformatics↗