Leveraging Polymer Therapeutics as Nanomedicine for Local Glioblastoma Immunotherapy

Research focusing on cancer immunotherapy has provided little progress toward improved survival rates for patients with glioblastoma (GBM), a poorly immunogenic tumor. Clinical trials for GBM immunotherapy primarily focus on the systemic administration of therapeutics; however, they have shown limited therapeutic success. The blood-brain barrier, the tumor immune microenvironment (TIME), the extracellular matrix, the highly invasive/proliferative nature of GBM, and intra- and inter-patient heterogeneity represent challenges to immunotherapy success. Administering polymer therapeutics as a class of biodegradable nanomedicines for localized treatment − a concept I pioneered − represents a less explored area that may fulfill the potential of GBM immunotherapy while reducing doses and adverse systemic effects.GLIOMERS aims to design an immunomodulatory brain-penetrating polymeric drug delivery system that will exploit its intrinsic therapeutic effect by synergizing with conjugated chemotherapeutic agent(s) to directly stimulate antitumor immunity. By encompassing different biomaterials properties, hybrid nanocarriers will be developed using a synthetic microfluidic-assisted approach based on chemically stabilized self-assembled hyaluronic acid – as immunomodulator – with complementary poly-L-lysine to support brain penetration. I will capitalize on the properties of this new class of nanocarriers by conjugating chemotherapeutics re-purposed for immunotherapy. This approach will allow not only the local spread of the drug within the GBM, but also an additional rewiring of immunosuppressive TIME with an enhanced T cell-mediated immune response.GLIOMERS will provide an innovative advance in the design of translational nanomedicines for local brain delivery, contributing to enhanced immunotherapeutic efficacy for GBM treatment.