The following summary is “Activation of Adaptive and Innate Immune Cells via Localized IL2 Cytokine Factories Eradicates Mesothelioma Tumors” published in the December 2022 issue of Oncology by Nash et al.

Clinical value is restricted by pharmacokinetic difficulties, vascular leak syndrome, and other potentially fatal toxicities observed by patients, despite the fact that IL2 immunotherapy has the ability to induce immune-mediated tumor lysis via activation of effector immune cells. To increase therapeutic efficacy while decreasing systemic cytokine exposure, researchers designed a localized IL2 delivery method that is both therapeutically feasible and safe. This study used a mouse model of malignant mesothelioma to assess the therapeutic potential of IL2 cytokine factories. Complete blood count and serum chemistry analysis were used to evaluate the safety and translatability of the platform, while time-of-flight mass cytometry (CyTOF) was used to analyze changes in immune populations.

With the use of IL2 cytokine factories, IL2 concentrations may be increased by a factor of 150 in the local compartment, with only a small amount escaping into the systemic circulation. After 1 week of monotherapy, 80% of the AB1 tumor burden was decreased, and 7 of 7 mice showed complete tumor eradication and no evidence of recurrence when IL2 cytokine factories were coupled with anti-programmed cell death protein 1 (aPD1). Furthermore, CyTOF analysis showed an increase in CD69+CD44+ and CD69CD44+CD62L T cells, reduction of CD86PD-L1 M2-like macrophages, and a corresponding increase in CD86+PD-L1+ M1-like macrophages and MHC-II+ dendritic cells after treatment. 

Finally, the results of blood chemistry tests in rodents confirmed the lack of adverse effects from cytokine factory treatment and provided more support for its clinical viability. The therapeutic efficacy of anti-programmed death-1 (aPD1) checkpoint therapy was improved by the presence of IL2 cytokine factories, which resulted in the elimination of aggressive mice malignant mesothelioma tumors and protection against tumor recurrence. This research lends credence to trying out this IL2 delivery method in humans.

Finally, blood chemistry ranges in rodents demonstrated the safety of cytokine factory treatment and reinforced its potential for clinical use.