Dr Aerts on the Rationale for the DENIM Trial in Mesothelioma

Joachim G. J. V. Aerts, MD, PhD, professor, pulmonary oncology, head, Department of Pulmonary Medicine, Erasmus MC Cancer Institute, discusses the rationale for conducting the phase 3 DENIM trial (NCT03610360) in patients with mesothelioma, highlighting the importance of focusing investigational efforts onto the dendritic cells.

Data from the study were presented at the International Association for the Study of Lung Cancer (IASLC) 2023 World Conference on Lung Cancer. In the DENIM trial, investigators assessed the potential of an allogeneic dendritic cell vaccine maintenance therapy to stimulate immune responses in patients with mesothelioma.

Mesothelioma is a disease characterized by an overwhelmingly poor prognosis, Aerts begins. Despite the occasional positive responses seen in patients treated with PD-1 inhibitors, the majority of patients either do not respond to immunotherapy at all or experience only temporary benefits, Aerts explains. This limited success can be attributed to the apparent absence of robust immune activation within the tumor microenvironment, he notes. To address this unmet need, investigators embarked on a novel treatment approach aimed at stimulating immune activation by administering dendritic cells to patients, Aerts adds.

Dendritic cells represent the most potent antigen-presenting cells in the human body, he expands. Therefore, the investigators’ strategy involved loading dendritic cells with an antigen lysate containing specific mesothelioma antigens, he explains. The primary objective of the investigation was to trigger a robust immune response, with the hope of eliciting the activation of CD8-positive T cells, which are known for their antitumor capabilities, Aerts says. 

Overall, this treatment approach was driven by the recognition that conventional treatments have fallen short in harnessing the immune system's full potential against mesothelioma, Aerts continues. By leveraging dendritic cells and their remarkable antigen presentation abilities, investigators aimed to initiate a more effective and sustained immune response within patients, ultimately improving their prospects, Aerts concludes.