배준범 연구실

Unlike hematologic malignancies, solid tumors physically block the infiltration of immune cells due to a dense extracellular matrix (ECM) and high interstitial fluid pressure. Furthermore, the hypoxic and acidic microenvironment, along with immunosuppressive cells such as TAMs, Tregs, and MDSCs, neutralizes the activity of even those immune cells that manage to penetrate, limiting the efficacy of simply injecting potent immune cells. Therefore, our laboratory aims to remodel the immunosuppressive 'Cold Tumor' into an immune-friendly 'Hot Tumor' using cytokines or cell-based therapies. Through this remodeling, we strive to ensure that therapeutic agents and immune cells can reach the deep core of the tumor and exert sustained antitumor effects. One of the major cell type utilized by our laboratory is the Mesenchymal Stromal Cell (MSC). MSCs offer the advantage of being an abundant source, as they can be readily obtained from various tissues, including bone marrow, skin, and adipose tissue. When administered via peritumoral injection, MSCs exhibit strong tumor tropism, enabling the localized expression of therapeutic agents specifically within the tumor site. Furthermore, we have engineered these MSCs to overexpress NQO1, providing them with resistance against reactive oxygen species (ROS)-induced stress within the tumor microenvironment. This modification ensures higher persistence and enhanced survival of the cells upon delivery. Our laboratory is validating the therapeutic efficacy of MSCs and other cell therapeutics within the tumor microenvironment (TME) using various mouse models. We have confirmed that when MSCs are administered via peritumoral injection into tumor-bearing mice, the cytokines or therapeutic agents expressed by the MSCs are delivered in a tumor-spec