Apoorva Mirji
Pronouns: she/her
Research Mentor(s): Maria Castro
Co-Presenter:
Research Mentor School/College/Department: Neurosurgery / Medicine
Presentation Date: April 20
Presentation Type: Oral5
Session: Session 6 – 4:40pm – 5:30 pm
Room: Breakout room 6
Authors:
Presenter: 5
Abstract
Glioblastoma multiforme(GBM) is a primary brain tumor that is affected by the CXCL12(C-X-C Motif Chemokine Ligand) /CXCR4(C-X-C Motif Chemokine Receptor 4) signaling pathway. In order to provide effective therapeutic mediums for this type of tumor, this CXCR4 signaling must be blocked. In order to effectively block CXCR4 signaling to inhibit GBM proliferation, we sought to create a method to deliver the CXCR4 antagonist (AMD3100) so that it can effectively inhibit the CXCR4/CXCL12 pathway: through the development of synthetic protein nanoparticles(SPNPs) with the drug. Given we already know that a major obstacle in the prevention of GBM inhibition is the blood, brain, barrier, we explored how the systemic delivery of AMD3100 SPNPs affected the mechanisms of the CXCR4/CXCL12 pathway to change the immune microenvironment and hinder GBM progression. Through the implantation of GBM cells in mice and the systemic delivery of AMD3100 in the free form and in the form of nanoparticles, we demonstrated how AMD3100 was effective in blocking the CXCR4/CXCL12 pathway. We measured the weight of the tumors and how much of the drug was in the plasma and the brain tumors to determine its effectiveness in penetrating the obstacles to inhibition, such as the blood, brain barrier. We are still working to determine how effective AMD3100 is in crossing the blood brain barrier with the use of mathematical models. We have previously determined that AMD3100 is effective in preventing GBM proliferation by decreasing the amount of CXCR4+ monocytic myeloid-derived suppressor cells that infiltrate the tumor microenvironment. The development of these SPNPs, once the effectiveness of crossing the blood, brain, barrier is determined, this form of systemic delivery has implications in the human clinical aspect.
Biomedical Sciences, Interdisciplinary, Natural/Life Sciences
