Targeting DIPG with engineered macrophages
New ways of treating cancer using the body’s own immune system have been making big strides recently. Advancements in immunotherapy revolutionize the treatment of cancers. Adoptive transfer of engineered immune cells demonstrates significant anticancer efficacy. CAR (chimeric antigen receptor) receptors on engineered T cells enable them to better recognize and attack cancer cells. Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive and difficult-to-treat brain tumor that usually occurs in children. There is an urgent and pressing need for innovative and effective approaches to fight it. This research project primarily focuses on a type of immune cells called macrophages, which are white blood cells that can digest microbes, cancer cells, and other foreign substances. When cancer is present, certain types of immune cells called monocytes in the circulation are constantly recruited to the tumors, where they turn into macrophages. Tumor-associated macrophages represent the major immune cells in various solid tumors including DIPG. By blocking certain pathways in cancer cells that help them avoid being eaten by macrophages, or by boosting signals in macrophages that tell them to attack, we can potentially make the immune system better at destroying cancer. Therefore, targeting macrophages to induce their tumor-killing abilities represents a promising avenue for cancer immunotherapy against DIPG.
Project Goals
While a lot of efforts have been focused on modifying T cells for cancer treatment, using engineered macrophages is a new and promising approach that is just starting to be explored. Unlike T cells, macrophages are naturally designed to engulf and remove harmful cells, making them an exciting tool for cancer treatment. However, the potential of engineered macrophages in treating DIPG has never been investigated. In our previous work, we successfully developed specialized engineered macrophages that were highly effective at attacking cancer cells. Now, in this study, we aim to put the engineered macrophages to the test against DIPG and uncover the precise biological mechanisms that drive their cancer-fighting abilities. To do this, we will use multiple preclinical DIPG modelsthat vary in their expression of tumor-associated markers. First, we will evaluate how well our engineered macrophages can eliminate DIPG cells in these models. Then, we will dive deeper into the molecular pathways that control how these macrophages recognize and destroy cancer cells, ultimately refining and developing next-generation engineered macrophages with even greater precision and potency. By successfully completing this study, we hope to unlock fundamental insights into how immune cells and cancer cells interact. Our findings could not only pave the way for innovative macrophage-based treatments for DIPG but also open new doors for improving immunotherapy approaches across various cancers.
