New Investigator Grant Awarded to John Ligon

Diffuse intrinsic pontine glioma (DIPG) is an uncurable and fatal childhood brain cancer in desperate need of new effective treatments. Our research program developed a new treatment called RNA nanoparticle vaccines (RNA-NPs) to treat DIPG and other cancers. RNA-NPs are a personalized treatment that activates the body’s own immune system to recognize and kill cancer cells. This promising treatment has entered clinical trials in humans for adults with brain cancer, and we will soon expand these trials to children with another type of brain cancer, as well as patients with skin cancer (melanoma) and bone cancer (osteosarcoma). We have promising preliminary data that this treatment may also be effective against DIPG and are thus applying for funding to further determine whether RNA-NPs should be tested for children with DIPG as well.

Additionally, we propose experiments that will help us understand how RNA-NPs work across all cancer types. Currently, it is unknown which specific immune cells are activated to kill the cancer cells and where they come from—they could either be activated to come to the tumor from somewhere else, or they could already be present within the tumor when they become activated. Understanding the underlying mechanisms of how RNA-NPs work will be important to (1) find markers that help predict which patients are most likely to respond to treatment, (2) discover new ways to target and kill DIPG cancer cells, (3) and identifying other drugs which can be combined with RNA-NPs for even more effective therapy. These kinds of mechanistic insights are crucial to obtaining more funding, particularly from the NIH, to support future studies including human clinical trials.

We think (hypothesize) that RNA-NP treatment leads to specific immune subsets being activated from outside of the tumor and subsequently going to the tumor to ultimately lead to cancer cell killing. We will use two models to test this hypothesis, a mouse model of DIPG and a 3D model created with a bioprinter that is like a human tumor. Using the mouse model we will determine which immune cells are specifically activated by RNA-NPs and which immune cells are necessary to result in DIPG cell killing.