News & Events
06/18/18
The GINAKIT2 Phase 1 clinical trial will test a new form of cancer immunotherapy
The GINAKIT2 Phase 1 clinical trial will test a new form of cancer immunotherapy that uses natural killer T (NKT) cells to fight neuroblastoma (NB) in children. This study will be the first in history to use genetically engineered NKT cells in humans.
 
Research in our laboratory has shown that NKTs naturally localize to the tumor site and that their presence in primary tumors correlates with favorable outcomes in NB patients. We have also found that NKTs destroy specific cells known as a tumor-associated macrophages (TAMs), which support growth and survival of NB cells.
 
To enable NKTs to directly kill NB tumor cells, we have engineered them to display a chimeric antigen receptor (CAR) on their surface. The CAR is composed of several building blocks originating from different sources that together help redirect the NKT cell toward a chosen target. In this case, CARs include a domain specific for the GD2 molecule, which is present at high levels in many NB tumors and has already led to promising results in clinical trials of GD2-targeted T cells in NB patients. In order to help NKT cells expressing the GD2-CAR (CAR.GD2 NKTs) last longer in patients, we included a domain that makes a mediator known as interleukin-15. This important molecule promotes NKT cell survival and function within tumor tissues.
 
We hypothesize that CAR.GD2-IL15 NKTs will demonstrate anti-tumor activity in NB patients through a combination of directly killing NB cells and indirectly targeting supportive TAMs. Our study will rigorously evaluate the safety of this approach, its efficacy, and determine how long CAR.GD2-IL15 NKTs can be detected in the human body.