Expand and pull: long-acting IL-7 and oncolytic virus to treat glioblastoma

Glioblastoma (GBM) is a brain tumor that causes neurological deterioration and death in most patients within 2 years. The long-term goal of this project is to develop a new treatment approach for GBM, by expanding peripheral effector immune cells with interleukin (IL)-7, and recruiting them into the tumor microenvironment with an oncolytic virus. In mouse models of GBM, we have observed an increase in survival when we combine long- acting IL-7 with oncolytic virus. Our central hypothesis is that combination therapy (a) improves CD8+ T cell trafficking to the TME, expansion, and anti-tumor function; (b) decreases myeloid and T regulatory cell driven immunosuppression in the TME; and (c) is effective when paired with standard-of-care radiation. Collectively, we term this concept “expand and pull” (expanding the immune system, recruiting it to the TME, and activating an anti-tumor response), and we will pursue it in two Aims. First, we will determine how long-acting IL-7 plus oncolytic virus therapy improves CD8+ T cell brain trafficking and function, and how it alters the tumor microenvironment. Second, we will determine whether long-acting IL-7 plus oncolytic virus therapy enhances standard-of-care outcomes and generates tumor infiltrating lymphocytes (TILs) that can treat recurrence. If successful, Aim 1 will determine the mechanism(s) by which IL-7 plus oncolytic therapy is effective, (and establish ways to improve it), and Aim 2 will promote translation to a clinical trial. Project Number: 1R01CA305974-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Cancer Institute (NCI) | Principal Investigator: Milan Chheda | Institution: WASHINGTON UNIVERSITY, SAINT LOUIS, MO | Award Amount: $645,185 | Activity Code: R01 | Study Section: Special Emphasis Panel[ZRG1 CDPT-C (08)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11391425