Nanomedicine Makes Big Strides in the Fight Against Breast Cancer

Immunotherapy is a monumental treatment for cancer treatment by harnessing the immune system's defense mechanisms. While promising, immunotherapy has not yet lived up to its potential partly due to an inability to adequately deliver drugs directly to tumors. Immunotherapeutic agents are systemically administered, but only a small amount penetrates the tumor where therapeutically relevant local immune infiltrates are found. To be effective, immunotherapy must be able to modulate this tumor immune microenvironment (TIME).

To achieve this, researchers led by Alessandro Grattoni, PhD, Chair of the Department of Nanomedicine, and co-corresponding author Corrine Ying Xuan Chua, PhD, Assistant Professor of Nanomedicine, developed a drug-agnostic nanofluidic implant to deliver immunotherapy within the tumor, providing a mechanism for sustained and controlled intratumoral dosing. In a study published recently in Nano Today, the team successfully delivered immunotherapy directly into triple-negative breast cancer (TNBC) tumors with nanofluidic implants, achieving tunable and sustained dosing of immunotherapeutics with high anti-tumor activity. Current methods of immunotherapy delivery to tumors rely primarily on direct bolus injection, which rapidly disseminates from the tumor, making it difficult to determine optimal dosing. Chua explained these strategies inherent limitations, “Effective local delivery necessitates precise injection into the tumor and hinges on confining drugs locally for an extended duration.” As an alternative, the team presents an implant strategy that sustainably releases controlled dosing of drugs intratumorally. A nanofluidic membrane controls diffusive drug elution from the implant reservoir, which abrogates rapid drug elimination from the tumor and maximizes immunotherapy localization. Ultimately, this could enable optimization of intratumoral immunotherapy regimens and improve patient outcomes. To ensure clinical relevance, the researchers explored intratumoral sustained release through their nanofluidic implant in EMT6 and 4T1 murine models of TNBC using a variety of immunotherapeutic agents with demonstrated anti-tumor activity, including agonist CD40 monoclonal antibody (mAb), anti-programmed death ligand-1 (PDL1) mAb, a polymeric prodrug of Stimulator of Interferon Genes (STING) agonist, and a polymeric prodrug of Toll-Like Receptor 7/8 (TLR 7/8) agonist (Resiquimod, R848).

Their results show the implant achieved sustained release of the immunotherapeutics tested as well as sustained intratumoral drug localization of agonist CD40 Ab and anti-PDL1 Ab in the 4T1 TNBC model. In addition, they demonstrated highly effective anti-tumor efficacy with radiation therapy and sustained intratumoral co-delivery of agonist CD40 Ab and anti-PDL1 Ab in the EMT6 TNBC model. They also achieved strong inhibition of 4T1 tumor growth with sustained intratumoral delivery of the STING or Resiquimod polymeric prodrugs.

“Our goal is to transform the way cancer is treated,” said Grattoni. “Overall, our technology represents a clinically relevant drug-agnostic therapeutic platform for the analysis of sustained intratumoral immunotherapy dosing.” Research is ongoing to further assess the safety and efficacy of this technology. And though it’s not quite ready for clinical trials, the researchers would like this to become a viable option for cancer patients in the future. Follow Grattoni’s team and their progress on social media.