While the discovery made by the Nobel Prize winners of 2018 is greatly promising when it comes to fighting against cancer, there are some setbacks to consider. Firstly, antibodies are costly to produce; hence they don't appeal to all patients. Secondly, antibodies are too large to penetrate through a solid tumor; therefore, the treatment falls behind, affecting all parts of the cancer.
"Post-doctoral researcher Dr. Rita Acúrcio started with thousands of molecular structures, and by using computer-aided drug design models and databases, we narrowed down the list of candidates until we reached the best structure," says Prof. Satchi-Fainaro. "First of all, the cost: since the antibody is a biological rather than a synthetic molecule, it requires a complex infrastructure and considerable funds to produce, costing about $200,000 per year per patient. In contrast, we have already synthesized the small molecule with simple equipment, in a short time and at a fraction of the cost.
Methods: In this study, we followed a transdisciplinary approach to discover novel small molecules that can modulate PD-1/PD-L1 interaction. To that end, we employed in silico analyses combined with in vitro, ex vivo, and in vivo experimental studies to assess the ability of novel compounds to modulate PD-1/PD-L1 interaction and enhance T-cell function.