The use of living tumor cells producing IL-۲ and GM-CSF as a new therapeutic approach to change the immunosuppressive tumor microenvironment in glioblastoma

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor, standing with a poor prognosis and treatment prospective. The GBM’s tumor microenvironment is highly complicated and immunosuppressive and the lack of T cells in the GBM’s Tumor microenvironment (TME) accounts for further malignant consequences. Therefore, immunotherapeutic strategies can be an efficient resolution to tackle with GBM. However, accessing to core cells of solid tumors always face with rigid challenges that hamper immunologic cells' functionality. Therefore, the ability of homing in tumors and penetrate into internal layers of tumor cells is a critical characteristics that new immunologic strategies must have. Recently, the prominent homing ability of living tumor cells into maternal tumor cells hold many attentions and engineering them to produce important cytokines against tumor have been showed promising results in treating solid tumors. Due to the immune function of IL-۲ against tumors, it can be used as an appropriate option as therapeutic approach. In addition, GM-CSF can balance the role of IL-۲ in TME and promote presentation function of dendritic cells. Moreover, inducing DCs’ functions results in generating memory and can act as a vaccine, which can extirpate minimal residual diseases (MRD) and decrease the risk of recurrence. In this article, we hypothesized that engineering living tumor cells expressing IL-۲ with GM-CSF can induce tumor-specific systemic immune responses and memory against GBM tumor. Additionally, contriving a safety switch in living tumor cells can prevent their wild expansion and hyperactivity and guarantee the safety of applying this strategy in clinic. Overall, this study is a preclinical investigation that can demonstrate the therapeutic potential of using engineered living tumor cells to therapeutically treat tumors and to convert the immunosuppressive tumor microenvironment (TME) into an immunostimulatory TME. In addition, it offer a personalized cellular therapy for patients with resistant solid cancers such as glioblastoma.

کلیدواژه ها:

Glioblastoma IL-۲ ، GM-CSF ، Cell Engineering ، Tumor Microenvironment