Novel combination immunotherapy for pancreatic cancer: potent anti-tumor effects with CD40 agonist and interleukin-15 treatment
Jonas RM Van Audenaerde, Elly Marcq, Bianca von Scheidt, Ashleigh S Davey, Amanda J Oliver, Jorrit De Waele, Delphine Quatannens, Jinthe Van Loenhout, Patrick Pauwels, Geert Roeyen, Filip Lardon, Clare Y Slaney, Marc Peeters, Michael H Kershaw, Phillip K Darcy, Evelien LJM Smits
Clinical and Translational Immunology | WILEY | Published : 2020
Objectives: With the poorest 5-year survival of all cancers, improving treatment for pancreatic cancer is one of the biggest challenges in cancer research. We sought to explore the potential of combining both priming and activation of the immune system. To achieve this, we combined a CD40 agonist with interleukin-15 and tested its potential in pancreatic cancer. Methods: Response to this combination regimen was assessed in pancreatic ductal adenocarcinoma mouse models, and a thorough analysis of the tumor microenvironment was performed. Results: We demonstrated profound reduction in tumor growth and increased survival of mice with the majority of mice being cured when both agents were combin..View full abstract
Awarded by Kom op tegen Kanker (Stand up to Cancer), the Flemish cancer society
We thank Celine Merlin, Christophe Hermans, Hilde Lambrechts, Hans De Reu, Viki Milovac, Esther Bartholomeus, Arvid Suls and Kaushalya Amarasinghe for their technical assistance, and Dr Paul Beavis, Dr Sherly Mardiana, Dr Eva Lion and Dr Hans Prenen for their scientific insights and advice. We express our special gratitude to Mr Willy Floren and the Vereycken family for their kind gifts which enabled us to perform this work. JRMVA was a research fellow of the Research Foundation Flanders (fellowship number 1S32316N) and has an Emmanuel van der Schueren grant funded by Kom op tegen Kanker (Stand up to Cancer), the Flemish cancer society. He received a travel grant from the Research Foundation Flanders (V4.090.17N) to visit the PeterMacCallum Cancer Centre and obtained a fellowship from the University of Antwerp (Rosa Blanckaert Foundation) to perform experiments. DQ and JVL are research fellows of the University of Antwerp, and EM is a postdoctoral researcher supported by Kom op tegen Kanker (Stand Up to Cancer), the Flemish cancer society. JDW was a research fellow of the Research Foundation Flanders (fellowship number 1121016N) and is currently a postdoctoral researcher supported by Kom op tegen Kanker (Stand Up to Cancer), the Flemish Cancer Society.