Figure 1.

The cytokine factories developed by Nash and colleagues consist of polymer encapsulated human retinal pigmented epithelial cells engineered to stably express mouse IL-2 (RPE-mIL2) or human IL-2 (RPE-hIL2). Xenogeneic engineered cells are protected from the host immune system by alginate hydrogel microencapsulation. In vivo, engineered cells secrete IL-2 and cytokine molecules escape from the pores of the hydrogel via diffusion. As demonstrated in a mouse model of mesothelioma, these cytokine factories enable controlled IL-2 secretion in a local compartment with limited leakage into the systemic circulation. Through recruitment and activation of the innate and adaptive immune systems against tumor cells, these cytokine factories were shown to be safe and effective as either a monotherapy or as an enhancer of novel checkpoint inhibitor potency. In the future, these cytokine factories have the potential to be translated to the clinic for the treatment of mesothelioma and other localized solid tumors.