Developing and testing multi-targeted immunomodulatory nanoparticles for treatment of high-risk neuroblastoma.”
Mentor Name: Prabhani Atukorale
The aggressive nature of pediatric neuroblastoma can be linked to the complex tumor microenvironment’s anti-therapeutic nature. Currently, only 15-25% of patients respond effectively to checkpoint-mediated immune cell therapy. To address this, our project focuses on altering the tumor microenvironment to favor T cell therapy.
The surrounding tumor environment of neuroblastoma and other childhood metastatic tumors is an active contributor to cancer progression. Using suppressive mechanisms like the creation of a dense, low-oxygen, acidic environment, these tumors create a physical and chemical barrier against therapy. This encourages a non-responsive effect to T cell therapy since the cells are now unable to merge with the tumor. This environment, known as “cold tumors,” poses an issue for clinicians.
Scientists are currently exploring ways to change this environment to become less shielded, allowing T cells and other immunotherapeutic treatments to enter the tumor and become effective. This environmental change, “from cold to hot,” is known to help treat metastasis.
Current studies have shown the clinically-effective uptake of nanoparticles in cold tumors (Rodallec et al., 2018). In drug delivery research, these nanoparticles have adjusted the environment to preserve patient immunity and deliver anti-cancer agents. Overall, this boosts the results of immune cell therapy.
Our project will explore using lipid-based nanoparticles combined with immunological agents. We will observe how effectively the tumor will take in the particle and also analyze how this can increase T cell response in mice with neuroblastoma. This will provide future directions on how clinicians can effectively treat pediatric cancers.
